Creativity (Ideas) Management in Industrial R&D Organizations: A Crea‐Political Process Model and an Empirical Illustration of Corus RD&T

Creativity management is a crucial topic to consider in the debate about the innovative research department. Against the background of discussions about individual creativity and organizational commitment, this article argues that the creative process in organizations is a matter of political strategies. The ideator literally has to sell his/her idea. The article therefore comes up with a crea‐political process model in which there is ample room for the thought that ideas emerge and survive within a social‐political context. In addition, the crea‐political process model is used to analyse the way in which the Corus Group Research Development and Technology (RD&T) department has implemented an electronic idea‐management system. The system, called eureka!, has been designed as a straightforward platform to capture, review, evaluate and select creative ideas. The findings challenge the literature on idea management in organizations to consider the political activities of ideators in the whole process of creativity.     

A novel genetic selection system for improved enantioselectivity of Bacillus subtilis lipase A

In directed evolution experiments, success often depends on the efficacy of screening or selection methods. Genetic selections have proven to be extremely valuable for evolving enzymes with improved catalytic activity, improved stability, or with altered substrate specificity. In contrast, enantioselectivity is a difficult parameter to select for. In this study, we present a successful strategy that not only selects for catalytic activity, but for the first time also for enantioselectivity, as demonstrated by the selection of Bacillus subtilis lipase A variants with inverted and improved enantioselectivity. A lipase mutant library in an aspartate auxotroph Escherichia coli was plated on minimal medium that was supplemented with the aspartate ester of the desired enantiomer (S)-(+)-1,2-O-isopropylidene-sn-glycerol. To inhibit growth of less enantioselective variants, a covalently binding phosphonate ester of the opposite (R)-(-)-1,2-O-isopropylidene-sn-glycerol enantiomer was added as well. After three selection rounds in which the selection pressure was increased by raising the phosphonate ester concentration, a mutant was selected with an improved enantioselectivity increased from an ee of -29.6 % (conversion 23.4 %) to an ee of +73.1 % (conversion 28.9 %) towards the (S)-(+)-enantiomer. Interestingly, its amino acid sequence showed that the acid of the catalytic triad had migrated to a position further along the loop that connects beta7 and alphaE; this shows that the position of the catalytic acid is not necessarily conserved in this lipase.     

Directed evolution of Bacillus subtilis lipase A by use of enantiomeric phosphonate inhibitors: crystal structures and phage display selection

Phage display can be used as a protein-engineering tool for the selection of proteins with desirable binding properties from a library of mutants. Here we describe the application of this method for the directed evolution of Bacillus subtilis lipase A, an enzyme that has important properties for the preparation of the pharmaceutically relevant chiral compound 1,2-O-isopropylidene-sn-glycerol (IPG). PCR mutagenesis with spiked oligonucleotides was employed for saturation mutagenesis of a stretch of amino acids near the active site. After expression of these mutants on bacteriophages, dual selection with (S)-(+)- and (R)-(-)-IPG stereoisomers covalently coupled to enantiomeric phosphonate suicide inhibitors (SIRAN Sc and Rc inhibitors, respectively) was used for the isolation of variants with inverted enantioselectivity. The mutants were further characterised by determination of their Michaelis-Menten parameters. The 3D structures of the Sc and Rc inhibitor-lipase complexes were determined and provided structural insight into the mechanism of enantioselectivity of the enzyme. In conclusion, we have used phage display as a fast and reproducible method for the selection of Bacillus lipase A mutant enzymes with inverted enantioselectivity.     

Indoor visible mold and mold odor are associated with new‐onset childhood wheeze in a dose‐dependent manner

Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case‐control study involving 150 children with new‐onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new‐onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new‐onset wheezing in a dose‐dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new‐onset wheezing. The association between mold and new‐onset wheeze was not modified by atopic status, suggesting a non‐allergic association.     

Molecular mechanisms of toxicity of important food-borne phytotoxins

At present, there is an increasing interest for plant ingredients and their use in drugs, for teas, or in food supplements. The present review describes the nature and mechanism of action of the phytochemicals presently receiving increased attention in the field of food toxicology. This relates to compounds including aristolochic acids, pyrrolizidine alkaloids, beta-carotene, coumarin, the alkenylbenzenes safrole, methyleugenol and estragole, ephedrine alkaloids and synephrine, kavalactones, anisatin, St. John's wort ingredients, cyanogenic glycosides, solanine and chaconine, thujone, and glycyrrhizinic acid. It can be concluded that several of these phytotoxins cause concern, because of their bioactivation to reactive alkylating intermediates that are able to react with cellular macromolecules causing cellular toxicity, and, upon their reaction with DNA, genotoxicity resulting in tumors. Another group of the phytotoxins presented is active without the requirement for bioactivation and, in most cases, these compounds appear to act as neurotoxins interacting with one of the neurotransmitter systems. Altogether, the examples presented illustrate that natural does not equal safe and that in modern society adverse health effects, upon either acute or chronic exposure to phytochemicals, can occur as a result of use of plant- or herb-based foods, teas, or other extracts.     

Improving the Quality of Information Flows in the Backend of a Product Development Process: a Case Study

Considerable research has gone into designing effective product development processes. This, coupled with the increasing need for products that are able to deliver reliable, complex functionality with a high degree of innovation, presents a major challenge to modern day industries in the business of developing products. In order to incorporate relevant field experience in the design and manufacturing of new products, increasingly detailed information needs to be retrieved from the market in a very short amount of time. In one particular consumer electronics industry, business process models describing the information flow in the backend of the product development process indicated massive data loss and also serious data quality degradation. This paper attempts to show how such losses can be mitigated and also proposes a business model that can adequately capture information of a higher quality and in a more structured manner. The end result will be a product development process that provides better feedback on current product performance and is more responsive to future market needs. Copyright © 2005 John Wiley & Sons, Ltd.     

19F nuclear magnetic resonance as a tool to investigate microbial degradation of fluorophenols to fluorocatechols and fluoromuconates

A method was developed to study the biodegradation and oxidative biodehalogenation of fluorinated phenols by 19F nuclear magnetic resonance (NMR). Characterization of the 19F NMR spectra of metabolite profiles of a series of fluorophenols, converted by purified phenol hydroxylase, catechol 1,2-dioxygenase, and/or by the yeast-like fungus Exophiala jeanselmei, provided possibilities for identification of the 19F NMR chemical shift values of fluorinated catechol and muconate metabolites. As an example, the 19F NMR method thus defined was used to characterize the time-dependent metabolite profiles of various halophenols in either cell extracts or in incubations with whole cells of E. jeanselmei. The results obtained for these two systems are similar, except for the level of muconates observed. Altogether, the results of the present study describe a 19F NMR method which provides an efficient tool for elucidating the metabolic pathways for conversion of fluorine-containing phenols by microorganisms, with special emphasis on possibilities for biodehalogenation and detection of the type of fluorocatechols and fluoromuconates involved. In addition, the method provides possibilities for studying metabolic pathways in vivo in whole cells.     

Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy

OBJECTIVES: This study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization. BACKGROUND: Little is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium. METHODS: Sixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a > or =5% increase in LV ejection fraction (LVEF). RESULTS: Of the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/-8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (> or =4 biphasic segments) were 89% and 81%, respectively, at late follow-up. CONCLUSIONS: Serial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.     

EURECA: European-Japanese Microcalorimeter Array

The EURECA project aims to demonstrate technological readiness of a micro-calorimeter array for application in future X-ray astronomy missions, like Constellation-X, EDGE, and XEUS. The prototype instrument consists of a 5×5 pixel array of TES-based micro-calorimeters read out by two SQUID-amplifier channels using frequency-domain-multiplexing (FDM) with digital base-band feedback. The detector array is cooled by a cryogen-free cryostat consisting of a pulse tube cooler and a two stage ADR. Initial tests of the system at the PTB beam line of the BESSY synchrotron showed stable performance and an X-ray energy resolution of 1.5 eV at 250 eV for read-out of one TES-pixel only. Next step is deployment of FDM to read-out the full array. Full performance demonstration is expected end 2008.      

Thin Functional Zeolite Layer Supported on Infrared Resonant Nano-Antennas for the Detection of Benzene Traces

Infrared absorption spectroscopy is a powerful analytical tool that enables the identification of molecular species. The sensitivity of this technique, that is strongly limited by the small absorption cross-section of molecular vibration, can be greatly improved by resonant interaction with nano-antennas via the surface-enhanced infrared absorption (SEIRA) mechanism. However, most of the examples of SEIRA concern solid-state molecular layers adsorbed on the nano-antennas, while the detection of gas traces still remains elusive due to the spatial extent of the near-field that is used to amplify the molecular vibrations resonantly. Here, a hybrid system composed of a plasmonic nano-antenna array coupled with nanosized zeolite coating for detection of volatile organic compounds in the near field of the resonators is demonstrated. The concerted action of the coating and the nano-antennas enabled the authors to detect record traces of benzene (25 ppb) within 10 min. This approach may ultimately allow the fabrication of a compact system for rapid detection of pharmaceutical and biocompounds with high sensitivity and high selectivity.