Technological learning: towards an integrated model

The acquisition and growth of technological knowledge is fundamental to competitive advantage in the emerging knowledge economy. This article explores the notion of technological learning as a means of developing the capabilities that underpin long term sustainable innovation. The research project was designed to identify new ways of understanding learning in the context of technology-driven SMEs, so the methods employed were essentially inductive in nature. This has resulted in the development of a comprehensive framework comprising four inter-related knowledge categories (Identity, Direction, Capability, and Relationship), each of which has an associated learning process (learning by reflecting, learning by strategising, learning by doing, and learning by interacting). We argue that it is the interaction between these knowledge categories that generates the new insights that are essential to technological learning

A note on heat and mass transfer from a sphere in Stokes\ud flow at low Péclet number

We consider the low Péclet number, Pe ≪ 1, asymptotic solution for steady-state heat and mass transfer from a sphere immersed in Stokes flow with a Robin boundary condition on its surface, representing Newton cooling or a first-order chemical reaction. The application of van Dyke’s rule up to terms of O(Pe3) shows that the O(Pe3 log Pe) terms in the expression for the average Nusselt/Sherwood number are double those previously derived in the literature. Inclusion of the O(Pe3) terms is shown to increase significantly the range of validity of the expansion

Entropy and Barrier-Hopping Determine Conformational Viscoelasticity in Single Biomolecules

Biological macromolecules have complex and non-trivial energy landscapes, endowing them a unique conformational adaptability and diversity in function. Hence, understanding the processes of elasticity and dissipation at the nanoscale is important to molecular biology and also emerging fields such as nanotechnology. Here we analyse single molecule fluctuations in an atomic force microscope (AFM) experiment using a generic model of biopolymer viscoelasticity that importantly includes sources of local `internal' conformational dissipation. Comparing two biopolymers, dextran and cellulose, polysaccharides with and without the well-known `chair-to-boat' transition, reveals a signature of this simple conformational change as minima in both the elasticity and internal friction around a characteristic force. A calculation of two-state populations dynamics offers a simple explanation in terms of an elasticity driven by the entropy, and friction by barrier-controlled hopping, of populations on a landscape. The microscopic model, allows quantitative mapping of features of the energy landscape, revealing unexpectedly slow dynamics, suggestive of an underlying roughness to the free energy.Comment: 25 pages, 7 figures, naturemag.bst, modified nature.cls (naturemodified.cls

Nano–Bio Interactions: Nanomedicine and Nanotoxicology

The 21st century has truly become the age of nanotechnology. Nanomaterials, design strategies, and processing have already made a significant impact in areas of materials science and electronics, with many commercial applications already being available on the consumer market. However, the ability to manipulate material functions and interactions on a scale of tens of nanometers, e.g., biological subcellular organelles, may yet prove to have the most significant impact on human health and the environment

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans

A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. ISRCTN11327221. [Abstract copyright: Copyright: © 2019 Byrne CS et al.

Service organisation for the secondary prevention of ischaemic heart disease in primary care.

BACKGROUND: Ischaemic heart disease (IHD) is a major cause of mortality and morbidity and its prevalence is set to increase. Secondary prevention aims to prevent subsequent acute events in people with established IHD. While the benefits of individual medical and lifestyle interventions is established, the effectiveness of interventions which seek to improve the way secondary preventive care is delivered in primary care or community settings is less so. OBJECTIVES: To assess the effectiveness of service organisation interventions, identifying which types and elements of service change are associated with most improvement in clinician and patient adherence to secondary prevention recommendations relating to risk factor levels and monitoring (blood pressure, cholesterol and lifestyle factors such as diet, exercise, smoking and obesity) and appropriate prophylactic medication. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2007, Issue 4), MEDLINE (1966 to Feb 2008), EMBASE (1980 to Feb 2008), and CINAHL (1981 to Feb 2008). Bibliographies were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of service organisation interventions in primary care or community settings in populations with established IHD. DATA COLLECTION AND ANALYSIS: Analyses were conducted according to Cochrane recommendations and Odds Ratios (with 95% confidence intervals) reported for dichotomous outcomes, mean differences (with 95% CIs) for continuous outcomes. MAIN RESULTS: Eleven studies involving 12,074 people with IHD were included. Increased proportions of patients with total cholesterol levels within recommended levels at 12 months, OR 1.90 (1.04 to 3.48), were associated with interventions that included regular planned appointments, patient education and structured monitoring of medication and risk factors, but significant heterogeneity was apparent. Results relating to blood pressure within target levels bordered on statistical significance. There were no significant effects of interventions on mean blood pressure or cholesterol levels, prescribing, smoking status or body mass index. Few data were available on the effect on diet. There was some suggestion of a \u22ceiling effect\u22 whereby interventions have a diminishing beneficial effect once certain levels of risk factor management are reached. AUTHORS\u27 CONCLUSIONS: There is weak evidence that regular planned recall of patients for appointments, structured monitoring of risk factors and prescribing, and education for patients can be effective in increasing the proportions of patients within target levels for cholesterol control and blood pressure. Further research in this area would benefit from greater standardisation of the outcomes measured

Meta-analytic framework for efficiently identifying progression groups in highway condition analysis

The minimum message length two-dimensional segmenter (MML2DS) criterion is a powerful technique for road condition data analysis developed at the Nottingham Transportation Engineering Centre (NTEC), University of Nottingham. The criterion analyses condition data sets by simultaneously identifying optimum trends in condition progression, the position in time and space of maintenance interventions, longitudinal segments within links, and the error likelihood of each measurement. This is done in an unsupervised manner through classification and regression models on the basis of the minimum message length (MML) metric. Use of MML, however, often requires an exhaustive comparison of all possible models, which naturally raises considerable search-control issues. This is precisely the case with the MML2DS approach. This paper presents an efficient meta-analytic framework for controlling the generation of progression groups, which considerably reduces the search space before the application of MML2DS. This is achieved by identifying founder sets of longitudinal segments, around which families of segments are likely to be formed. An effective subset of these families is then selected, after which the MML2DS criterion is used as the final arbiter to determine ultimate model configurations and fits. This approach has proved to be very powerful, resulting in significant improvements in efficiency to the effect that accurate results are obtained in a few minutes where it previously took weeks with much smaller data sets. The indications are that this approach can be applied to other techniques besides MML2DS

B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen

Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides. Clinical GM2 vaccination studies for melanoma patients suggest that a human antibody response to SDa can be induced. Expression of porcine B4GALNT2 in human HEK293 cells results in increased binding of anti-SDa antibody and increased binding of Dolichos biflorus agglutinin (DBA), a lectin commonly used to detect SDa. In pigs, B4GALNT2 is expressed by vascular endothelial cells and endothelial cells from a wide variety of pig backgrounds stain with DBA, suggesting that porcine vascular expression of B4GALNT2 is not polymorphic. Mutations in B4GALNT2 have been engineered in mice and pigs. In both species, the B4GALNT2-KO animals are apparently normal and no longer show evidence of SDa antigen expression. Pig tissues with a mutation in B4GALNT2, added to a background of alpha-1,3-galactosyltransferase deficient (GGTA1-KO) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient (CMAH-KO), show reduced antibody binding, confirming the presence of B4GALNT2-dependent antibodies in both humans and non-human primates. Preclinical xenotransplantation using B4GALNT2-deficient donors has recently been reported. Elimination of this source of immunogenic pig antigen should minimize acute injury by preformed anti-pig antibody and eliminate an induced clinical immune response to this newly appreciated xenotransplantation antigen

Anderson Localization of Classical Waves in Weakly Scattering Metamaterials

We study the propagation and localization of classical waves in one-dimensional disordered structures composed of alternating layers of left- and right-handed materials (mixed stacks) and compare them to the structures composed of different layers of the same material (homogeneous stacks). For weakly scattering layers, we have developed an effective analytical approach and have calculated the transmission length within a wide region of the input parameters. When both refractive index and layer thickness of a mixed stack are random, the transmission length in the long-wave range of the localized regime exhibits a quadratic power wavelength dependence with the coefficients different for mixed and homogeneous stacks. Moreover, the transmission length of a mixed stack differs from reciprocal of the Lyapunov exponent of the corresponding infinite stack. In both the ballistic regime of a mixed stack and in the near long-wave region of a homogeneous stack, the transmission length of a realization is a strongly fluctuating quantity. In the far long-wave part of the ballistic region, the homogeneous stack becomes effectively uniform and the transmission length fluctuations are weaker. The crossover region from the localization to the ballistic regime is relatively narrow for both mixed and homogeneous stacks. In mixed stacks with only refractive-index disorder, Anderson localization at long wavelengths is substantially suppressed, with the localization length growing with the wavelength much faster than for homogeneous stacks. The crossover region becomes essentially wider and transmission resonances appear only in much longer stacks. All theoretical predictions are in an excellent agreement with the results of numerical simulations.Comment: 19 pages, 16 figures, submitted to PR