Understanding the metabolic burden of recombinant antibody production in Saccharomyces cerevisiae using a quantitative metabolomics approach

The cellular changes induced by heterologous protein expression in the yeast Saccharomyces cerevisiae have been analysed on many levels and found to be significant. However, even though high‐level protein production poses a metabolic burden, evaluation of the expression host at the level of the metabolome has often been neglected. We present a comparison of metabolite profiles of a wild‐type strain with those of three strains producing recombinant antibody variants of increasing size and complexity: an scFv fragment, an scFv–Fc fusion protein and a full‐length IgG molecule. Under producing conditions, all three recombinant strains showed a clear decrease in growth rate compared with the wild‐type strain and the severity of the growth phenotype increased with size of the protein. The levels of 76 intracellular metabolites were determined using a targeted (semi) quantitative mass spectrometry based approach. Based on unsupervised and supervised multivariate analysis of metabolite profiles, together with pathway activity profiling, the recombinant strains were found to be significantly different from each other and from the wild‐type strain. We observed the most prominent changes in metabolite levels for metabolites involved in amino acid and redox metabolism. Induction of the unfolded protein response was detected in all producing strains and is considered to be a contributing factor to the overall metabolic burden on the cells.     

Current condition and future directions for lean construction in highways projects: A small and medium-sized enterprises (SMEs) perspective

The aim of this study is to identify the parameters defining how Lean Construction (LC) is being implemented (current condition) and how LC can be further promoted (future direction) from a Small-Medium Sized Enterprises (SMEs) perspective. Although SMEs constitute the largest group in construction supply chains, LC, as an emerging phenomenon in civil construction project management, has been rarely investigated from an SMEs perspective. Also, overlooking the more macro factors like project governance and supply chain management, LC deployments have been mainly discussed from a production process perspective to date. After a review of the extant literature and 20 interviews with managers from the highways sector, a list of 31 current condition and 40 future direction statements were produced, classified under the delivery, process, training, project governance and supply chain related headings and used in a questionnaire survey with 110 responses. The current condition highlights problems like a short-term relations structure, competitive tendering mechanisms, fragmentation, problems in engaging with SMEs for LC, unstandardised LC techniques, and issues with convincing SMEs to deploy LC by demonstrating the business case on mutual benefits. Action items relating to the current project delivery structure were given the highest importance by the supply chain, alongside the LC training and project governance issues for the future of LC at highways SMEs. Additionally, a statistically significant correlation was identified among many future action items.     

Technology adoption in the BIM implementation for lean architectural practice

Justification for researchThe construction companies are facing barriers and challenges in BIM adoption as there is no clear guidance or best practice studies from which they can learn and build up their capacity for BIM use in order to increase productivity, efficiency, quality, and to attain competitive advantages in the global market and to achieve the targets in environmental sustainability.

Purpose

This paper aims to explain a comprehensive and systemic evaluation and assessment of the relevant BIM technologies as part of the BIM adoption and implementation to demonstrate how efficiency gains have been achieved towards a lean architectural practice.Design/methodology/approachThe research is undertaken through a KTP (Knowledge Transfer Partnership) project between the University of Salford and the John McCall Architects based in Liverpool, which is an SME (Small Medium Enterprise). The overall aim of KTP is to develop a lean design practice through the BIM adoption and implementation. The overall BIM implementation approach uses a socio-technical view in which it does not only consider the implementation of technology but also considers the socio-cultural environment that provides the context for its implementation. The technology adoption methodology within the BIM implementation approach is the action research oriented qualitative and quantitative research for discovery, comparison, and experimentation as the KTP project with JMA provides an environment for “learning by doing”.

Findings

Research has proved that BIM technology adoption should be undertaken with a bottom-up approach rather than top-down approach for successful change management and dealing with the resistance to change. As a result of the BIM technology adoption, efficiency gains are achieved through the piloting projects and the design process is improved through the elimination of wastes and value generation.

Originality/value

Successful BIM adoption needs an implementation strategy. However, at operational level, it is imperative that professional guidelines are required as part of the implementation strategy. This paper introduces a systematic approach for BIM technology adoption based on a case study implementation and it demonstrates a guideline at the operational level for other architectural companies of architectural practices.     

The effect of slightly warm temperature on work performance and comfort in open‐plan offices – a laboratory study

The aim of the study was to determine the effect of a temperature of 29°C on performance in tasks involving different cognitive demands and to assess the effect on perceived performance, subjective workload, thermal comfort, perceived working conditions, cognitive fatigue, and somatic symptoms in a laboratory with realistic office environment. A comparison was made with a temperature of 23°C. Performance was measured on the basis of six different tasks that reflect different stages of cognitive performance. Thirty‐three students participated in the experiment. The exposure time was 3.5 h in both thermal conditions. Performance was negatively affected by slightly warm temperature in the N‐back working memory task. Temperature had no effect on performance in other tasks focusing on psychomotor, working memory, attention, or long‐term memory capabilities. Temperature had no effect on perceived performance. However, slightly warm temperature caused concentration difficulties. Throat symptoms were found to increase over time at 29°C, but no temporal change was seen at 23°C. No effect of temperature on other symptoms was found. As expected, the differences in thermal comfort were significant. Women perceived a temperature of 23°C colder than men.     

Synthesis of cobalt nanoparticles to enhance magnetic permeability of metal–polymer composites

Metallic cobalt nanoparticles were synthesized by hydrogen reduction method. Particles were coated in situ with carbon by adding ethene to reaction flow. Particles were characterized by transmission electron microscopy, energy dispersive X-ray emission, X-ray diffraction, X-ray fluorescence and BET method. The observed cobalt particle size distributions in different cobalt batches produced with unvarying reaction parameters was reproducible: The mean diameter of primary cobalt particle varied only 5% from the mean value of 76 nm in different batches. Increased carbon precursor concentration decreased mean diameter of cobalt particles to 17 nm. The produced nanoparticles were used as filler material in 0–3 type metal–polymer composites. Composite samples with varying filler loading were fabricated with mixing extrusion and injection moulding techniques. The magnetic properties of the fabricated composites were measured up to 1 GHz. In order to analyse the particle distribution in composite matrix and its effect on magnetic properties the microstructure was studied.     

Forum The role of CIB: some reflections

An explanation for the low innovation activity in construction is put forward. The central argument is that the current theory of construction is one root cause for low innovation activity. Instead, an explicit and more powerful theory of construction is needed for further innovation, which is ‘to manage new ideas into good currency’. There are three main mechanisms in the current theory of construction which are identified as causing this hindrance. Firstly, production theories in general, as well as construction theories specifically, have been implicit. Therefore, it has not been possible to transfer radical managerial innovations, such as lean production, from manufacturing to construction at a theoretical level. Direct application of this production template to construction has been limited due to the different context of construction in comparison with manufacturing. Secondly, the current theoretical model of construction is based on the transformation model of production. It is argued that the principles of this model are counterproductive, because uncertainty and interdependence are abstracted away. This leads to fragmented and myopic management and inflated variability. Practical examples show that these deficiencies and related practical constraints hinder the implementation of top-down innovations. Thirdly, empirical research shows that also bottom-up innovations - systematic learning and problem solving - are being hindered by the current theory. Thus, the advancement of innovations in construction requires that a new, explicit and valid theory of construction is created, and business models and control methods are developed on the basis of that new theory. Cet article propose une explication concernant le taux bas de l'activité d'innovation dans la secteur du bâtiment. L'argument central étant que la théorie actuelle de la construction est une des raisons fondamentales de cette activité basse d'innover. Au lieu de cela, on a besoin d'une théorie de la construction explicite et plus efficace afin d'innover. Dans la théorie actuelle du bâtiment, il y a trois mécanismes fondamentaux qui sont identifiés comme causes gênant cette innovation. Premièrement, les théories de production en général, ainsi que les théories de la construction en particulier, ont été implicites. Ainsi, il était impossible de transférer des innovations gestionnaires radicales, comme la production allégée (lean production), à partir du domaine de la fabrication à celui du bâtiment à un niveau théorique. L'application directe de ce modèle de production au secteur bâtiment a été limitée à cause du contexte différent de celui-ci en comparaison de celui de la fabrication. Deuxièmement, le modèle théorique actuel de la construction bâtiment est basé sur le modèle de la transformation de production. On avance que les principes de ce modèle agissent négativement sur la productivité parce que l'incertitude et l'interdépendance en sont exclues. Ceci mène à une gestion fragmentée et myope ainsi qu'à une inflation de la variabilité. Des exemples pratiques montrent que ces déficiences et les contraintes pratiques qui leur sont liées, gênent les implémentations des innovations de haut en bas. Troisièmement, une étude empirique montre que les innovations de bas en haut - c'est-à-dire l'apprentissage systématique et la résolution de problèmes - sont gênés par la théorie actuelle. Ainsi, le progrès dan les innovations du secteur bâtiment exige qu'une nouvelle théorie explicite et valide soit créée, et que des modèles d'affaires et des méthodes de contrôle soient développés sur la base de cette nouvelle théorie.     

The North Karelia Project: a programme for community control of cardiovascular diseases

Patients with chronic glomerulonephritis and mild hypertension show a consistent behaviour in their renin-aldosterone-system. There is a close correlation between the elevation of mean blood pressure and destruction of glomeruli. No correlation has been found between renin values and the degree of hypertension. Thus the cuase of mild hypertension occurring in the early stages of chronic GN remains to be elucidated. Normal PRA values in spite of hypertension and expansion of ECFV accompaning progression of chronic glomerulonephritis could be a sign of "relative hyperreninemia". Apparently various mechanisms are involved in the pathogenesis of renal hypertension. These include sodium retention, increased cardiac output. anemia, renin, aldosterone, prostaglandins, expanded plasma volume and peripheral vasoconstriction. These factors are more or less active in the different stages of hypertension and renal failure.     

Chemical and physical properties of short rotation tree species

The European Union’s growth strategy (Europe 2020) requires reductions in greenhouse gas (GHG) emissions and increases in both renewable energy sources and energy efficiency. Short rotation forestry (SRF) has achieved greater awareness due to these targets. Short rotations (1–12 years), rapid growth and the ability to coppice are typical for SRF. Salix, Populus, Alnus and Betula have smaller GHG emissions of biomass production than annual agricultural plant species, since management and harvesting are not needed every year. Physicochemical properties of these species must be known when their utilisation is planned and optimised. Seven tree species were studied: three willows (Salix myrsinifolia, Salix schwerinii and Klara), one aspen (Populus tremula), one alder (Alnus glutinosa) and two birches (Betula pendula and Betula pubescens). One stem wood (S) sample and one stem wood and bark (SB) sample of each tree were investigated. Furthermore, seven surface soil samples and four incineration ash samples (two S. myrsinifolia and two S. schwerinii) were also studied. Heating values, densities, ash contents as well as carbon, hydrogen and nitrogen contents of all short rotation biomass samples were usually quite typical for the corresponding tree species. Additional observations included the accumulation of cadmium in willow and aspen samples, small chloride content values, and higher ash- and element contents in SB samples than in the corresponding S samples. Nutrient content of ash was usually higher in the S sample, contradictory to biomass samples, and finally the cadmium content of the ash samples was very high.     

Levels of mycotoxins and sample cytotoxicity of selected organic and conventional grain-based products purchased from Finnish and Italian markets

The contamination levels of 16 different Fusarium- and Aspergillus-mycotoxins were chemically determined from randomly selected organic and conventional grain-based products purchased from Finnish and Italian markets. The cytotoxicity of the samples was analyzed with an in vitro test using feline fetal lung cells. Overall, the concentrations of the mycotoxins studied were low in all of the samples. Enniatins B and B1 as well as deoxynivalenol were the most predominant mycotoxins in the samples, being present in 97%, 97%, and 90% of the samples, respectively. The geographical origin or the agricultural practice had no influence on the mycotoxin concentrations of the samples. The babyfoods included in the samples had significantly lower concentrations of mycotoxins than the other products with a mean total mycotoxin content of 47 microg/kg compared with 99 microg/kg for the other kinds of food. All the samples evoked toxicity in the in vitro test, but no correlation between cytotoxicity and the mycotoxin concentrations was observed.