Innovation Leaders Should be Controlled Schizophrenics

Innovating is a multi‐faceted process. In this paper, four different, yet intertwined aspects of this process are distinguished. The first aspect concerns the content of the innovation; a new product, a new technology or a new market. The second aspect concerns the group dynamics of the innovation team. The third aspect concerns seeing the innovation process as a creative process. And the fourth aspect has to do with leadership. Since these four aspects are simultaneously working together during the innovation process, the leaders of this process are working in a very difficult situation, as all four aspects need to be dealt with in different ways. Nearly all of them are, in one way or another, in conflict with one another. They may conflict in real actions, in time horizons (past, present or future) or in effect (positive reactions during market introduction do not garantee ultimate market success). This means that innovation leaders need to show a special kind of leadership. This leadership must be balanced, people‐focused and must include a high tolerance for ambiguity and paradoxes. They have to be nice and nasty at the same time. In short: innovation leaders should be some kind of controlled schizophrenics.     

Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serum

In several autoimmune disorders, including rheumatoid arthritis (RA), autoantibodies are thought to be the driving force of pathogenicity. Glycosylation of the Fc-part of human Igs is known to modulate biological activity. Hitherto, glycosylation of human IgG-Fc has been analyzed predominantly at the level of total serum IgG, revealing reduced galactosylation in RA. Given the pathogenic relevance of autoantibodies in RA, we wished, in the present study, to address the question whether distinct Fc-glycosylation features are observable at the level of antigen-specific IgG subpopulations. For this purpose, we have developed a method for the microscale purification and Fc-glycosylation analysis of anti-citrullinated peptide antibodies (ACPA). ACPA represent a group of autoantibodies that occur with unique specificity in RA patients. Their presence is associated with increased inflammatory disease activity and rapid joint destruction. Results indicate that ACPA of the IgG1 subclass vary considerably from total serum IgG1 with respect to Fc-galactosylation, with galactosylation being higher on ACPA than on serum IgG1 for some patients, while other patients show higher galactosylation on serum IgG1 than on ACPA. Using this method, studies can be performed on the biological and clinical relevance of ACPA glycosylation within RA patient cohorts.     

Generation of time delays: simplified models of intracellular signalling in cerebellar Purkinje cells

In many neuronal systems, information is encoded in temporal spike patterns. The recognition and storage of temporal patterns requires the generation and modulation of time delays between inputs and outputs. In cerebellar Purkinje cells, stimulation of metabotropic glutamate receptors (mGluRs) results in a delayed calcium and voltage response that has been implicated in classical conditioning and temporal pattern recognition. Here, we analyse and simplify a complex model of the intracellular signalling network that has been proposed as a substrate for this delayed response. We systematically simplify the original model, present a minimal model of time delay generation, and show that a delayed response can be produced by the combination of negative feedback and autocatalysis, without any intervening signalling steps that would contribute additive delays. The minimal model is analysed using phase plane methods, and classified as an excitable system. We discuss the implication of excitability for computations performed by intracellular signalling networks in general.     

The use of interorganisational ICT in United States construction projects

In recent research, the use of ICT applications in real time construction projects have been documented and analysed extensively. However, there is a need for identifying and analysing in-depth the mechanisms influencing the use of interorganisational ICT applications and for solutions to eliminate potential barriers to the successful use of ICT. A model is developed providing insights in these mechanisms. Based on this model and expert interviews in the United States construction industry directions for solutions to barriers to the successful use of interorganisational ICT — document management applications, workflow management applications, and product modelling applications — in construction projects are formulated. These solutions focus on stimulating the personal motivation to use ICT, the external motivation to use this technology, and facilitating conditions in terms of knowledge and skills and acting opportunities to use ICT.     

Improved creaminess of low-fat yoghurt: The impact of amylomaltase-treated starch domains

Amylomaltase-treated starch (ATS) is an excellent creaminess enhancer in yoghurt. Small amounts of ATS raised the creaminess perception of low-fat yoghurt (1.5%) to that of full-fat yoghurt (5%). In this way, a reduction in fat-related energy value could be achieved from 45 to 21.5 kcal/100 g product. The functionality of ATS in set yoghurt resulted from discrete domains of ATS that resemble the microstructural behaviour of fat particles. The microstructure of the yoghurt is dominated by the protein and the ATS domains are enclosed in or bound to this protein network. The perceived creaminess resulted from in-mouth melting of these ATS domains due to a combined effect of their physical melting and hydrolysis by amylase present in the saliva.     

The effect of dendritic topology on firing patterns in model neurons

Neuronal firing patterns are influenced by both membrane properties and dendritic morphology. Distinguishing two sources of morphological variability-metrics and topology-we investigate the extent to which model neurons that have the same metrical and membrane properties can still produce different firing patterns as a result of differences in dendritic topology. Within a set of dendritic trees that have the same number of terminal segments and the same total dendritic length, we show that firing frequency strongly correlates with topology as expressed by the mean dendritic path length. The effect of dendritic topology on firing frequency is bigger for trees with equal segment diameters than for trees whose segment diameters obey Rall's 3/2 power law. If active dendritic channels are present, dendritic topology influences not only firing frequency but also type of firing (regular, bursting).     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Size, differentiation and the performance of Dutch daily newspapers

We demonstrate how organizational ecology can contribute tostrategic management and managerial practice by using resource-partitioningtheory to make predictions with respect to: (i) the short-runperformance (i.e. growth and profitability) consequences ofbroad (generalist) vis-à-vis focus (specialist) strategies;(ii) the detrimental performance implications of a particularinstance of being strategically ‘stuck in the middle’;and (iii) the performance consequences of organizational sizedifferences. We hypothesize that these effects depend on theposition of the organization in resource space. These predictionsare tested by estimating models of growth and profitability,using data on Dutch generalist (national) and specialist (regional)newspapers from 1968 to 1994. The findings show that resource-partitioningtheory provides a dynamic backbone to understand the performanceconsequences of different generic strategies and organizationalsize positions.     

On-line coupling of high-performance liquid chromatography to a continuous-flow enzyme assay based on electrospray ionization mass spectrometry

Liquid chromatography (LC) was coupled on-line to a continuous-flow enzymatic assay using electrospray ionization mass spectrometry (ESI-MS) as readout for the screening of enzyme inhibitors in complex samples. Inhibitors were detected by changes in the concentration of the enzymatic reaction products, indicating the inhibition of enzymatic activity. The molecular masses of the inhibitors were determined with high certainty by using retention time matching and peak shape comparison. Due to the high matching accuracy, baseline separation of coeluting analytes was not necessary in order to identify the correct masses of the bioactive compounds. The continuous-flow system was successfully applied for the screening of complex samples, such as natural extracts. For a red clover extract, detection limits of 0.3-0.8 micromol/L were obtained. System validation was performed by determining the IC(50) values of four inhibitors in the flow-injection mode. The IC(50) values were in the 0.11-5.6 micromol/L range and correspond closely to data obtained by microtiter plate assays. Detection limits were in the range of 0.018-0.35 micromol/L in the flow-injection mode, and 0.075-0.75 micromol/L in the LC mode. These values are well below the typical compound concentrations (1-10 micromol/L) used in high-throughput screening. Together with an interday precision of 12.6%, these results demonstrate the applicability of the system for bioactivity screening of complex mixtures, generating both chemical and biological information on bioactive compounds in a single run.