An experience of modularity through design

We aim to utilise the experiences of a marine industry-based design team to determine the need for research into a modular design methodology in an industrial environment. In order to achieve this we couple the outcome of a current design project with the findings of a recent literature survey with the objectives of firstly, clarifying why a methodology is required and, secondly, defining the key elements which the methodology would have to realise or address. The potential benefits of modularity have long been recognised in the shipbuilding industry. Many shipbuilders adopt a 'module' approach to ship construction whereby the ship structure is separated into a number of large structural 'blocks' to ease manufacture and manoeuvrability during construction. However, as understanding of the capabilities of modularity as a design tool develops there is increased interest in capitalising on the differing life phase benefits of modularity such as reduced design costs and time, increased ease of maintenance, upgrade, re-use, redesign and standardisation across individual products and product families. This is especially pertinent in naval shipbuilding where the maintenance of a class of ship requires that all previously designed ships in that class must be of similar outfitting and must be able to interface with the new ship, in terms of propulsion, weapons, communications and electronics, and thus often require some form of retrofit. Therefore, many shipbuilders are moving from viewing modularity as a purely 'manufacturing' principle to a design centred principle. However, as noted by Chang and Ward 'none of the design theories or tools in the mechanical world serves as an articulate procedure for designers to follow in practising modular design'. Thus, despite the identification of a need to introduce modular principles at an earlier stage than detail design and construction, there is little aid in the form of tools, techniques and methodologies for designers in practice

Effect of Crack Blunting on Subsequent Crack Propagation

Theories of toughness of materials depend on an understanding of the characteristic instabilities of the crack tip, and their possible interactions. In this paper we examine the effect of dislocation emission on subsequent cleavage of a crack and on further dislocation emission. The work is an extension of the previously published Lattice Greens Function methodology. We have developed a Cavity Greens Function describing a blunt crack and used it to study the effect of crack blunting under a range of different force laws. As the crack is blunted, we find a small but noticeable increase in the crack loading needed to propagate the crack. This effect may be of importance in materials where a dislocation source near the crack tip in a brittle material causes the crack to absorb anti-shielding dislocations, and thus cause a blunting of the crack. It is obviously also relevant to cracks in more ductile materials where the crack itself may emit dislocations.Comment: LaTeX, 8 pages, 4 Postscript figures included as uuencoded gzipped tar file. To appear in Mat. Res. Soc. Symp. Proc. Also available at http://nils.wustl.edu/schiotz/papers/MRS-Fall-95.htm

Amikacin concentrations and target ranges for mycobacterial infection

The aim of this research is to determine whether amikacin dosage guidelines for multi - drug resistant mycobacterial infections achieve peaks of 35 - 45 mg/L (OD) or 65 - 80 mg/L (TW) and troughs <5 mg/L

Session V. Miscellaneous Discussion

In the few minutes we have left before adjourning this session, I\u27d like to review briefly various points that have been made this morning. The development of a failure predictive technology evidently involves a proper combination of several ingredients. These include a quantitative measurement capability, a proper description of the mechanisms of failure, a way to combine these elements into a probabilistic failure predictor that takes account of the variance in both the above quantities, a way to include a priori data that may exist which will help to sharpen the prediction, and finally, a way so that management choices (which govern the cost-risk tradeoffs) can be injected into the predictions. This morning we have heard a number of talks relating to one of the above items, i.e., the mechanisms of failure in metallic materials with an emphasis upon fatigue processes including fatigue initiation, crack growth mechanisms, and complications that are introduced by consideration of the fully plast.ic problem

A Multi-Scale Theoretical Scheme for Metal Deformation

A conceptual theoretical scheme for single crystal metal deformation is presented consisting of multi-scale models from dislocation dynamics to the continuum constitutive relations. The scheme rests on the fundamental observations that deformation is characterized by partially ordered internal dislocation wall structures, discontinuous strain bursts in time, and strain localization in a surface slip band structure. A percolation strain model corresponds to elementary slip line burst events, with percolation parameters to be supplied from experiments and dislocation dynamics studies of wall structures. A model for localization of the slip lines into bands is proposed (for suitable loadings) which envisions channels for slip formed from the dense planar walls (otherwise called GNB's). A rudimentary continuum model is constructed from the outputs of these models which consists of two principal internal variables, and exhibits the desired hardening behavior with strain. The continuum model is based on two different material properties in the slip bands, and in the matrix between the bands. The scheme does not yet include mechanisms for the underlying dislocation ordering or patterning, but addresses the transport of dislocations through these (presumably known) structures

Whole exome sequencing reveals diverse genomic relatedness between paired concurrent endometrial and ovarian carcinomas

IntroductionConcurrent non-serous endometrial and ovarian tumours are often managed clinically as two separate primary tumours, but almost all exhibit evidence of a genomicrelationship.MethodologyThis study investigates the extent of relatedness using whole exome sequencing,which was performed on paired non-serous endometrial and ovarian carcinomas from27 patients with concurrent tumours in a cohort with detailed clinicopathologicalannotation. Four whole exome sequencing-derived parameters (mutation, mutationalburden, mutational signatures and mutant allele tumour heterogeneity scores) wereused to develop a novel unsupervised model for the assessment of genomic similarityto infer genomic relatedness of paired tumours.ResultsThis novel model demonstrated genomic relatedness across all four parameters in alltumour pairs. Mutations in PTEN, ARID1A, CTNNB1, KMT2D and PIK3CA occurredmost frequently and 24 of 27 (89%) tumour pairs shared identical mutations in at leastone of these genes, with all pairs sharing mutations in a number of other genes.Ovarian endometriosis, CTNNB1 exon 3 mutation, and progression and death fromdisease were present across the similarity ranking. Mismatch repair deficiency wasassociated with less genomically similar pairs.DiscussionAlthough there was diversity across the cohort, the presence of genomic similarity in allpaired tumours supports the hypothesis that concurrent non-serous endometrial andovarian carcinomas are genomically related and may have arisen from a commonorigin

Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy

Land degradation neutrality: testing the indicator in a temperate agricultural landscape

Land degradation directly affects around 25% of land globally, undermining progress on most of the UN Sustainable Development Goals (SDG), particularly target 15.3. To assess land degradation, SDG indicator 15.3.1 combines sub-indicators of productivity, soil carbon and land cover. Over 100 countries have set Land Degradation Neutrality (LDN) targets. Here, we demonstrate application of the indicator for a well-established agricultural landscape using the case study of Great Britain. We explore detection of degradation in such landscapes by: 1) transparently evaluating land cover transitions; 2) comparing assessments using global and national data; 3) identifying misleading trends; and 4) including extra sub-indicators for additional forms of degradation. Our results demonstrate significant impacts on the indicator both from the land cover transition evaluation and choice or availability of data. Critically, we identify a misleading improvement trend due to a trade-off between improvement detected by the productivity sub-indicator, and 30-year soil carbon loss trends in croplands (11% from 1978 to 2007). This carbon loss trend would not be identified without additional data from Countryside Survey (CS). Thus, without incorporating field survey data we risk overlooking the degradation of regulating and supporting ecosystem services (linked to soil carbon), in favour of signals from improving provisioning services (productivity sub-indicator). Relative importance of these services will vary between socioeconomic contexts. Including extra sub-indicators for erosion or critical load exceedance, as additional forms of degradation, produced a switch from net area improving (9%) to net area degraded (58%). CS data also identified additional degradation for soil health, including 44% arable soils exceeding bulk density thresholds and 35% of CS squares exceeding contamination thresholds for metals

Changing contexts and critical moments: interim outcomes for children and young people living through involuntary relocation

The aim of this article is to understand how involuntary relocation – in the context of transformational regeneration – affects children and young people’s (CYP) interim outcomes through its impacts on residential contexts, and its intersections with their transitions and critical moments. Findings are based on a longitudinal qualitative study of 13 families’ (comprising 32 CYP) lives as they relocated from high rise flats to different housing and neighbourhoods over three years. Relocation altered two key contexts directly, home and neighbourhood, and may have indirectly altered the other contexts – peers, school and family. However, we found there were as many non-relocation related factors as relocation factors associated with outcomes, and a number of significant critical moments affecting CYP’s lives. Whilst relocation can seem the ‘big thing’ from the point of view of practitioners and researchers, from the perspective of CYP, it can seem a small part of the much bigger picture of change in their lives