Long-chain fatty ammonium quaternaries in papermaking

A series of long-chain quaternary ammonium halogen esters (UKK-chemicals), quaternary dimethyl tallow epoxypropyl ammonium halogens (EPK1), quaternary ditallow methyl epoxypropyl ammonium halogens (EPK2), and EPK2 oligomers (EPK2P) were synthesized. At acidic, neutral, or slightly basic conditions, EPK1-, EPK2-, EPK2P-, and UKK-chemicals operate as cationic chemicals. They can be used, for example, as stock sizings, surface sizings, or fixatives. Stock sizing, surface sizing, and fixative experiments indicate that EPK1-, EPK2-, EPK2P-, and UKK-chemicals function at least as well as or better than the corresponding synthetic chemicals used in papermaking.     

System approach to modeling of liver glucose metabolism with physiologically interpreted model parameters outgoing from [18F]FDG concentrations measured by PET

New mathematical models from physiologically interpreted parameters capable of evaluating glucose metabolism within the liver and/or the whole body were developed. The group of pigs in a fasting state and the group of pigs with euglycemic supraphysiological hyperinsulinemia were scanned by positron emission tomography after a single dose of [(18)F]FDG tracer. Simultaneously frequent sampling of the dynamic data of [(18)F]FDG plasma concentration in artery, portal vein and hepatic vein was obtained. A system approach to the liver and/or the whole-body system by the tools of linear dynamic sysztem theory was used. Three kinds of structural models, single input and single output or multiple outputs and multiple inputs and single output, were identified. Differences between the group of fasting pigs and the group of pigs in euglycemic supraphysiological hyperinsulinemia were identified by estimated parameters of the structural models. The suitability of the structural mathematical models for the estimation of physiologically interpreted parameters from PET was validated.     

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.     

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.     

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.     

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.     

Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

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.     

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.