Design synthesis and shape generation

If we are to capitalise on the potential that a design approach might bring to innovation in business and society, we need to build a better understanding of the evolving skill-sets that designers will need and the contexts within which design might operate. This demands more discourse between those involved in cutting edge practice, the researchers who help to uncover principles, codify knowledge and create theories and the educators who are nurturing future design talent. This book promotes such a discourse by reporting on the work of twenty research teams who explored different facets of future design activity as part of Phase 2 of the UK's research council supported Designing for the 21st Century Research Initiative. Each of these contributions describes the origins of the project, the research team and their project aims, the research methods used and the new knowledge and understanding generated. Editor and Initiative Director, Professor Tom Inns, provides an introductory chapter that suggests ways the reader might navigate these viewpoints. This chapter concludes with an overview of the key lessons that might be learnt from this collection of design research activity

Ultrafast self-gating Bragg diffraction of exploding nanocrystals in an X-ray laser

In structural determination of crystalline proteins using intense femtosecond X-ray lasers, damage processes lead to loss of structural coherence during the exposure. We use a nonthermal description for the damage dynamics to calculate the ultrafast ionization and the subsequent atomic displacement. These effects degrade the Bragg diffraction on femtosecond time scales and gate the ultrafast imaging. This process is intensity and resolution dependent. At high intensities the signal is gated by the ionization affecting low resolution information first. At lower intensities, atomic displacement dominates the loss of coherence affecting high-resolution information. We find that pulse length is not a limiting factor as long as there is a high enough X-ray flux to measure a diffracted signal

Spatial grammar implementation: from theory to useable software

Currently available computer-aided design tools provide strong support for the later stages of product development processes where the structure and shape of the design have been fixed. Support for earlier stages of product development, when both the structure and shape of the design are still fluid, demands conceptual design tools that support designers' ways of thinking and working, and enhance creativity, for example, by offering design alternatives, difficult or not, possible without the use of such tools. The potential of spatial grammars as a technology to support such design tools has been demonstrated through experimental research prototypes since the 1970s. In this paper, we provide a review of recent spatial grammar implementations, which were presented in the Design Computing and Cognition 2010 workshop on which this paper is based, in the light of requirements for conceptual design tools and identify future research directions in both research and design education

Proteomic analysis identifies key differences in the cardiac interactomes of dystrophin and micro-dystrophin

ΔR4-R23/ΔCT micro-dystrophin (μDys) is a miniaturized version of dystrophin currently evaluated in a Duchenne muscular dystrophy (DMD) gene therapy trial to treat skeletal and cardiac muscle disease. In pre-clinical studies, μDys efficiently rescues cardiac histopathology, but only partially normalizes cardiac function. To gain insights into factors that may impact the cardiac therapeutic efficacy of μDys, we compared by mass spectrometry the composition of purified dystrophin and μDys protein complexes in the mouse heart. We report that compared to dystrophin, μDys has altered associations with α1- and β2-syntrophins, as well as cavins, a group of caveolae-associated signaling proteins. In particular, we found that membrane localization of cavins −1 and − 4 in cardiomyocytes requires dystrophin and is profoundly disrupted in the heart of mdx^{5cv} mice,a model of DMD. Following cardiac stress/damage, membrane-associated cavin-4 recruits the signaling molecule ERK to caveolae, which activates key cardio-protective responses. Evaluation of ERK signaling revealed a profound inhibition, below physiological baseline, in the mdx^{5cv} mouse heart. Expression of μDys in mdx^{5cv} mice prevented the development of cardiac histopathology but did not rescue membrane localization of cavins nor did it normalize ERK signaling. Our study provides the first comparative analysis of purified protein complexes assembled in vivo by full-length dystrophin and a therapeutic micro-dystrophin construct. This has revealed disruptions in cavins and ERK signaling that may contribute to DMD cardiomyopathy. This new knowledge is important for ongoing efforts to prevent and treat heart disease in DMD patients

Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis.

To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis. Retrospective review of PCR, IVCM and culture results for MK diagnosis at Moorfields Eye Hospital between August 2013 and December 2014. Results PCR results were available for 259 MK patients with concurrent culture for 203/259 and IVCM for 149/259. Sensitivities and specificities with 95% confidence intervals [95% CI] were calculated for Acanthamoeba keratitis (AK) and fungal keratitis (FK), by comparison with culture, for both IVCM and PCR. For AK, FK and bacterial keratitis (BK) sensitivities were calculated, for each diagnostic method, by comparison with a composite reference standard (a positive result for one or more of culture, PCR or IVCM having a specificity of 100% by definition). For the latter, sensitivities with [95% CI] were: for AK, IVCM 77.1% [62.7-88.0%], PCR 63.3% [48.3-76.6%], culture 35.6 [21.9-51.2]; for FK, IVCM 81.8% [48.2-97.7%], PCR 30.8% [9.09-61.4%], culture 41.7% [15.2-72.3%]; for BK, PCR 25.0% [14.7-37.9%], culture 95.6% [87.6-99.1%]. Conclusion IVCM was the most sensitive technique for AK and FK diagnosis but culture remains our gold standard for BK. These findings reflect results to be expected from service providers to UK ophthalmology units and demonstrates the need at our centre for ongoing diagnostic result audit leading to the potential to improve PCR diagnosis. Both FK and AK are now common in the UK; ophthalmology units need to have all these techniques available to optimise their MK management

Selectivity control during the single-step conversion of aliphatic carboxylic acids to linear olefins

We have studied the single-step catalytic conversion of biomass-derived aliphatic carboxylic acids to linear olefins via tandem hydrogenation/dehydration reactions. Hexanoic acid was converted to a mixture of hexenes (92.0% selectivity) over silica–alumina supported Cu nanoparticles. Remarkably, we observed a rapid selectivity switch to 99.8% hexane once carboxylic acids were fully consumed, with similar results using butanoic acid derived from biomass using consolidated bioprocessing. Based on intermediate, desorption, and in situ spectroscopy studies, we propose that the presence of a small amount of carboxylic acid on the catalyst surface leads to a dramatic decrease in overhydrogenation of olefins

Innovation in tourism: Re-conceptualising and measuring the absorptive capacity of the hotel sector

Recent reviews of research on innovation in tourism have highlighted a number of weaknesses in the literature. Among these is the limited theorising and empirical investigation of innovative practices by tourism organisations. This paper responds to these concerns by examining one important dimension of innovation within commercial tourism organisations, namely their ability to acquire, assimilate and utilise external knowledge (absorptive capacity) for competitive advantage. The topic is pertinent because there is evidence to suggest that tourism organisations are particularly dependent on external sources of knowledge when compared with businesses in other sectors. Following a discussion of the conceptual antecedents of absorptive capacity and its dimensions, a validated instrument for its measurement is developed and used to measure the absorptive capacity of the British hotel sector. The results suggest that current conceptions of absorptive capacity have limitations when applied to tourism enterprises. Absorptive capacity is re-conceptualised to overcome these deficiencies. The research and policy implications of the findings are discussed. © 2014 Elsevier Ltd