Towards an understanding of the impact of resources on the design process

Considerable effort has been devoted within the design research community to understanding the structure of design processes and their development for different design problems. Whilst much work has examined the impact of design goals upon the structure of a design process, less attention has been paid to the role that design resources can play. This paper describes an experiment directed towards gaining an understanding of the impact that both active resources (which perform design tasks) and passive resources (which are used by active resources) can have upon design process structure. Main outcomes from the experiment were the conclusive identification that resources can significantly impact design process structure and a number of examples of how these impacts manifest themselves. The main conclusion of the paper is that given the sizeable impact resources can have upon process structure, there is a considerable need to obtain a greater understanding of these impacts to facilitate the development of techniques that can support design process definition based upon an understanding of the design resources being used to solve a design problem

Developing and applying an integrated modular design methodology within a SME

Modularity within a product can bring advantages to the design process by facilitating enhanced design reuse, reduced lead times, decreased cost and higher levels of quality. While the benefits of modularity are becoming increasingly better known, at present it is usually left to the designers themselves to introduce modularity into products. Studies into modularity have shown that byimplementing 'formal' methods, further benefits can be made in terms of time, cost, quality and performance. Current approaches that have been proposed for the formal development of modular design methodologies fail to accurately represent knowledge that is inherently produced during design projects and fail to consider design from the different viewpoints of the development process. This work, built on previous work on modularity and design for reuse, aims to develop an integrated design methodology that will optimise the modules created through the design process and allow for modularity to be 'built-in' to product development from the initial stages. The methodology andassociated tools have been developed to provide an easy-to-use approach to modularity that has support for design rationales and company knowledge that aid in effective design decision making. The methodology, named GeMoCURE, provides an integrated total solution to modular design based on reuse of proven physical and knowledge modules. Its incremental nature allows for the optimalstructure to be maintained as the design progresses. A special focus has been on the application of this approach for Small to Medium Enterprises (SMEs), which are typically challenged by a lack of design human resources and expertise

All-cause and liver-related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

BACKGROUND High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. METHODS We obtained information from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. RESULTS Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer, 1.87 (1.61-2.17) for any circulatory disease, and 9.40 (7.00-12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment. CONCLUSIONS People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality

The S-Cycle performance matrix : supporting comprehensive sustainability performance evaluation of technical systems

The work reported in this paper consolidates and rationalises disparate evaluation methods in a novel, generic framework to support the selection of comprehensive material/energetic sustainability performance indicators (SPIs) for technical systems. The S-Cycle Performance Matrix (S-CPMatrix) is comprised of 6 generic sustainability goals, 11 SPI archetypes, and 23 corresponding metrics identified from a model of technical system sustainability (the S-Cycle). The matrix was evaluated by interpreting and classifying 324 indicators currently applied to evaluate technical system sustainability performance in the literature, with 94.1% found to be fully classifiable with respect to the matrix following several refinements. The remaining 5.9% suggested additional SPI archetypes and a goal that were not initially identified. The matrix is intended to support decision makers in meeting three criteria for comprehensiveness identified from the literature: (C1) inclusion of indicators measuring performance at all relevant scales; (C2) inclusion of efficiency and effectiveness indicators; and (C3) coverage of all system sustainability goals. It may be applied to different systems in conjunction with different evaluation methods, thereby contributing to more consistent guidance on the selection of comprehensive SPIs for technical systems. In addition to industrial evaluation and comparison with existing evaluation methods, four avenues for future research were identified: (i) use of the S-CPMatrix to support systems comparison/benchmarking; (ii) further investigation of unsupported metrics; (iii) the nature and measurement of contaminants; and (iv) the comprehensiveness of SPI sets currently used in sustainability performance evaluation of technical systems

Identification of basepairs within Tn5 termini that are critical sfor H-NS binding to the transpososome and regulation of Tn5 transposition

<p>Abstract</p> <p>Background</p> <p>The H-NS protein is a global regulator of gene expression in bacteria and can also bind transposition complexes (transpososomes). In Tn5 transposition H-NS promotes transpososome assembly <it>in vitro </it>and disruption of the <it>hns </it>gene causes a modest decrease in Tn5 transposition (three- to five-fold). This is consistent with H-NS acting as a positive regulator of Tn5 transposition. Molecular determinants for H-NS binding to the Tn5 transpososome have not been determined, nor has the strength of the interaction been established. There is also uncertainty as to whether H-NS regulates Tn5 transposition <it>in vivo </it>through an interaction with the transposition machinery as disruption of the <it>hns </it>gene has pleiotropic effects on <it>Escherichia coli</it>, the organism used in this study.</p> <p>Results</p> <p>In the current work we have further examined determinants for H-NS binding to the Tn5 transpososome through both mutational studies on Tn5 termini (or 'transposon ends') and protein-protein cross-linking analysis. We identify mutations in two different segments of the transposon ends that abrogate H-NS binding and characterize the affinity of H-NS for wild type transposon ends in the context of the transpososome. We also show that H-NS forms cross-links with the Tn5 transposase protein specifically in the transpososome, an observation consistent with the two proteins occupying overlapping binding sites in the transposon ends. Finally, we make use of the end mutations to test the idea that H-NS exerts its impact on Tn5 transposition <it>in vivo </it>by binding directly to the transpososome. Consistent with this possibility, we show that two different end mutations reduce the sensitivity of the Tn5 system to H-NS regulation.</p> <p>Conclusions</p> <p>H-NS typically regulates cellular functions through its potent transcriptional repressor function. Work presented here provides support for an alternative mechanism of H-NS-based regulation, and adds to our understanding of how bacterial transposition can be regulated.</p

The contribution of diet and genotype to iron status in women:a classical twin study

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04)

Notch signaling in serous ovarian cancer

Ovarian cancer is the most lethal of all gynecologic malignancies because women commonly present with advanced stage disease and develop chemotherapy refractory tumors. While cytoreductive surgery followed by platinum based chemotherapy are initially effective, ovarian tumors have a high propensity to recur highlighting the distinct need for novel therapeutics to improve outcomes for affected women. The Notch signaling pathway plays an established role in embryologic development and deregulation of this signaling cascade has been linked to many cancers. Recent genomic profiling of serous ovarian carcinoma revealed that Notch pathway alterations are among the most prevalent detected genomic changes. A growing body of scientific literature has confirmed heightened Notch signaling activity in ovarian carcinoma, and has utilized in vitro and in vivo models to suggest that targeting this pathway with gamma secretase inhibitors (GSIs) leads to anti-tumor effects. While it is currently unknown if Notch pathway inhibition can offer clinical benefit to women with ovarian cancer, several GSIs are currently in phase I and II trials across many disease sites including ovary. This review will provide background on Notch pathway function and will focus on the pre-clinical literature that links altered Notch signaling to ovarian cancer progression

High-Resolution Electron Time-of-Flight Apparatus for the Soft-X-Ray Region

A gas-phase time-of-flight (TOF) apparatus, capable of supporting as many as six electron-TOF analyzers viewing the same interaction region, has been developed to measure energy- and angle-resolved electrons with kinetic energies up to 5 keV. Each analyzer includes a newly designed lens system that can retard electrons to about 2% of their initial kinetic energy without significant loss of transmission; the analyzers can thus achieve a resolving power (E/ΔE) greater than 104 over a wide kinetic-energy range. Such high resolving power is comparable to the photon energy resolution of state-of-the-art synchrotron–radiation beamlines in the soft x-ray range, opening the TOF technique to numerous high-resolution applications. In addition, the angular placement of the analyzers, by design, permits detailed studies of nondipolar angular distribution effects in gas-phase photoemission

Angle-Resolved Photoelectron Spectroscopy of C60

Angle-resolved photoelectron spectra of gaseous C60 were recorded in the photon energy regions from 21 to 108 eV and from 295 to 320 eV. Partial cross sections σ and the angular distribution anisotropy parameter β vary significantly with photon energy, particularly in the near-threshold region of the valence and the core ionization regimes. Some of these effects may be attributed to scattering of the outgoing photoelectron by the atoms of the ionized C60 molecule. Our results indicate that the observed satellites of the C(1s) main line are most likely of shake-up character. Low-energy electrons emitted below the shake-off threshold indicate the occurrence of K-shell vacancy filling double Auger decay