Application of generic principles of process intensification to solution crystallization enabled by a task-based design approach

The design of current industrial crystallizers is strongly focussed on optimization of known types of crystallization equipment. These crystallizers harbour various physical phenomena, which are strongly entangled. The application of generic principles of process intensification (PI) to crystallization processes requires individual control over physical phenomena. A new design method is applied that exploits elementary processing functions as building blocks for design instead of existing equipment, which enables the application of generic principles of PI. Innovations in the field of crystallization to manipulate shear forces, manipulate nucleation rates with external fields, and improve control over solvent removal with membranes are key technologies. A case study demonstrates the application of task-based design for solution crystallization. The results show how task-based design leads to high modularization of the process representation and model architecture. In addition, task-based design enables the application of generic PI principles, which results in a large flexibility to manipulate final product quality. Future needs include generalization of task-based design for crystallization and development of novel technologies for single task manipulation.     

The impact of a call centre on communication in a programme and its projects

Call centres are increasingly being utilised in public sector programmes to facilitate and manage communication between numerous stakeholders. Yet, the impact of call centres on projects has not been investigated. This paper reports on a survey with 92 respondents that assessed the impact of a call centre for a repair and maintenance programme. An empirically verified model is presented to illustrate the relationship between call centre communication and project performance. A balance of frequent informal and formal communication is shown to reduce mistrust and conflict of interest resulting from each party trying to maximise his respective economic position in the principal–agency relationship. The data provides evidence that a call centre improves the communication, collaboration and trust in project principal–agency relationships which, in turn, is perceived to contribute to project performance.     

Explosive vapor bubble growth in uniformly superheated liquids: R-113 and mercury

Based on experimental and analytical work conducted previously with R-113, the results of an analytical study of the vapor bubble dynamics for mercury associated with nucleation and growth are presented here. The simulations show that a growing mercury vapor bubble can be substantially unstable under sufficiently high superheat, as with a superheat level of 100 °C, and that surface tension tends to stabilize the process. At a superheat level of 30 °C, the growth is marginally stable due to the high surface tension, and quite stable in the very early stages of the growth. For most cases, the wavelength of growing perturbations appear to be relatively large compared to that for water, again due to the large surface tension of mercury. As a result of the high liquid-to-vapor density ratio, the growth rates of mercury vapor bubbles can be quite high, reaching a diameter of 1 m in 1 s, with an initial superheat of 100 °C and pressure of 0.1 atm. The effects of system pressure are also considered here.     

Comparison of the chronic toxicity of piroxantrone, losoxantrone and doxorubicin in spontaneously hypertensive rats

We have determined the time course, the spatial spread in brain tissue, and the intracellular distribution of biotin- and fluorescein-labeled phosphorothioate oligodeoxynucleotides (ODNs) following single injections into the rat striatum or the lateral ventricle. These time and space parameters were correlated with the ability of c-fos phosphorothioate antisense ODNs to suppress the induction of Fos protein by cocaine. A rapid and dose-dependent tissue penetration of labeled ODNs was observed following either intrastriatal or intraventricular injections of a constant sample volume. Inspection of tissue sections by confocal microscopy uncovered a distinct change in the intracellular disposition of labeled ODNs during the 24 h post-injection period. At 1, 6 and 12 h, the vast majority of the fluorescent signal was confined to the interstitial spaces throughout the zone penetrated by ODNs. Neuronal nuclei displayed faint labeling along the outer portion of the nucleus at 1 and 6 h post-injection. At these time-points, ODNs were not detected in the cytoplasm. By 16 h, ODNs were barely detectable in the extracellular space and absent from neuronal nuclei. Instead, ODNs were seen in large cytoplasmic granules of neurons throughout the tissue zone penetrated by the ODNs. Experiments with intrastriatal injections of antisense ODNs to c-fos mRNA revealed Fos suppression between 3 and 12 h, but not at 16 and 24 h. This combined analysis has revealed that (1) restricted tissue penetration by ODNs limits their antisense effects on protein expression, and (2) depletion of extracellular ODNs and sequestration of c-fos antisense ODNs into large intracellular granules coincides with the loss of their biological activity.     

Prodrug esters of the indolocarbazole CEP-751 (KT-6587)

Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials.     

Pattern classification using projection pursuit

This article discusses the adaptation of recently developed regression techniques to classifier design. Apart from finite sample effects, projection pursuit (PP) regression may be used to model a desired response (class) as a sum of ridge functions according to a minimum expected squared error criterion. This approach can be shown to furnish an optimal discriminant function which can satisfy the Neyman-Pearson criterion over all possible thresholds. Basis function expansions are used instead of smoothed histograms to reduce computation. Since good approximation of a discriminant by a linear combination of moderate number of ridge functions may not be easy, we introduce an improved method utilizing a nonlinear weighting function.     

Molecular dynamics simulations as a tool for improving protein stability

Haloalkane dehalogenase (DhlA) was used as a model protein toexplore the possibility to use molecular dynamics (MD) simulationsas a tool to identify flexible regions in proteins that canserve as a target for stability enhancement by introductionof a disulfide bond. DhlA consists of two domains: an     

Increased globotriaosylceramide in familial dysautonomia

Familial Dysautonomia (FD) is an autosomal recessive disease of unknown etiology, occurring primarily in Ashkenazi Jews. Patients are neurologically impaired, with deficits primarily in autonomic and sensory functions. The biochemical and genetic defects have remained elusive, precluding carrier detection and prenatal diagnosis. High-performance liquid chromatography data indicated up to a threefold increase in the neutral glycosphingolipid globotriaosylceramide in Dysautonomic fibroblasts and lymphoblasts. Total ganglioside values, measured by colorimetric, fluorometric or specific sodium borohydride incorporation, were decreased. Affected fibroblasts exhibited a range of pleomorphic phenotypes, such that the usual swirl-like confluent growth pattern of normal fibroblasts was distorted to varying degrees, suggesting abnormalities in the FD plasma membrane, possibly affecting cell-cell contacts. The glycosphingolipid increase could not be accounted for on the basis of markedly decreased α-galactosidase activity, as in Fabry's disease, where patients also display decreased autonomic function.