Structural and electrophysiological analysis of annexin V mutants. Mutagenesis of human annexin V, an in vitro voltage-gated calcium channel, provides information about the structural features of the ion pathway, the voltage sensor and the ion selectivity filter

Annexin V binds to phospholipids in a calcium-dependent manner and exhibits calcium channel activity in vitro. We prepared a variety of mutants yielding information about the structure-function relationship of the ion channel activity. All mutants were characterized by X-ray crystallography, electron microscopy and electrophysiological measurements. Their structures are insignificantly changed whereas their electrophysiological properties are drastically different. Glu95, located in the central hydrophilic pore of the molecule, is crucial for the ion selectivity filter as its exchange leads to reduced calcium and increased sodium conductance. The removal of Glu17, located on the protein surface and far from the ion conduction pathway, leads to the appearance of a second conductance level of 9 pS in addition to the conductance level of about 30 pS in the wild-type molecule. This was also the case for Glu78, which is part of a weak calcium binding site. The exchange of Glu17 and Glu78 produced a mutant retaining only the smaller conductance level. We conclude that these two residues influence the angle between the two halves of the molecule, which determines the diameter of the ion conduction pathway, thereby leading to the occurrence of a second conductance level.     

Determination of carbon black fillers in vulcanizates of natural rubber by metathesis degradation

A method for the determination of carbon black fillers in peroxide vulcanizates or sulfur vulcanizates of natural rubber (NR, cis-1,4-polyisoprene) by metathesis degradation with 1-octene was developed using the catalyst WCl₆? (C₂H₅)₃Al₂Cl₃. The carbon black was separated from the reaction mixture by centrifuging and determined by weighing. In this connection, investigations were also performed with the catalyst WCl₆? C₂H₅Al₂Cl₃ which was less suitable for filler determination. The rate of degradation of crosslinked NR with (E)-4-octene was measured. Metathesis reactions of 2-methyl-2-pentene (low-molecular-weight model compound of NR) with 7-tetradecene showed the importance of double bond shift for the degradation of NR.     

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.     

A scheme to randomly generate surface dust points for the 3D complex variable boundary element method (CVBEM)

A scheme to randomly generate dust points on the surface of a three-dimensional (3D) object is proposed. This scheme will potentially eliminate the bias of a density of points which are approximately equally spaced on the surface, as well as eliminate possible weighting requirements for areas of higher density. This method has the potential to reduce computational effort, as fewer points might be required to define the surface area. The global trial function vector can be assigned to these dust points and then entered into the complex variable boundary element method (CVBEM) commercial code. This scheme can be applied to each piece of a system that is comprised of a connected multiple geometry. A noticeable benefit of this approach is that the same problem can be studied several times, using a new random distribution of surface points each time. The smallest error can then be determined and that run selected. The Mathematica code used to generate the scheme is attached as an appendix.     

A Multiagent System for the Reliable Execution of Automatically Composed Ad-hoc Processes

This article presents an architecture to automatically create ad-hoc processes for complex value-added services and to execute them in a reliable way. The uniqueness of ad-hoc processes is to support users not only in standardized situations like traditional workflows do, but also in unique non-recurring situations. Based on user requirements, a service composition engine generates such ad-hoc processes, which integrate individual services in order to provide the desired functionality. Our infrastructure executes ad-hoc processes by transactional agents in a peer-to-peer style. The process execution is thereby performed under transactional guarantees. Moreover, the service composition engine is used to re-plan in the case of execution failures. The work presented in this article was supported by the Swiss National Science Foundation as part of the project MAGIC (FNRS-68155), as well as by the Swiss National Funding Agency OFES as part of the European projects KnowledgeWeb (FP6-507482) and DIP (FP6-507483). Authors in alphabetic order     

Entschwefelung von gerührtem und ungerührtem Roheisen mit kalkreicher Schlacke unter oxidierender Gasatmosphäre

Aus Betriebsergebnissen bei der Pfannenentschwefelung ist ein negativer Einfluß oxidierender Gasphasen bekannt. Daher war es das Ziel der eigenen Untersuchungen in einer geeigneten Apparatur die Wirkung oxidierender Bedingungen in der Gasphase sowohl auf den Verlauf des Schwefelabbaues in der Schlacke als auch des Schwefeltransportes aus dem Roheisen in die Schlacke zu untersuchen. Oxidierende Gasphasen erwirken bei der Pfannenentschwefelung an der Phasengrenze Schlacke/Gas eine Oxidation des Schwefels aus der Schlacke, ohne jedoch bei ruhender Schlackenschicht ein Oxidationspotential in der Schlacke aufzubauen, das bis zur Phasengrenze Roheisen/Schlacke durchgreift und dort die Entschwefelung des Roheisens durch die Siliciumgehalte stört. Sowohl die Entschwefelung des Roheisens als auch die Oxidation des Schwefels aus der Schlacke werden durch höhere Temperaturen und durch eine Rührwirkung gefördert. Der Schwefeltransport wird bei den ungerührten wie bei den gerührten Schmelzen durch Diffusionsvorgänge gesteuert und auch hier durch steigende Temperaturen und rührende Kräfte begünstigt.     

Synthesis of Aminopyridazines from Aminocyclopropenylium Salts and Diazomethyl Compounds [1]

Amino-substituted cyclopropenylium salts ( 11a,b ) react with diazomethyl compounds ( 12a-i ) in dichloromethane or acetonitrile in the presence of a base (ethyldiisopropylamine, 1,5-diazabicyclo[4.3.0] non-5-ene) to form 4-aminopyridazines ( 13a-i ) specifically. The reaction is interpreted in terms of an initial electrophilic diazoalkane substitution to give diazomethylcyclopropenes ( 11 + 12 → 14 ) which undergo a [1.5]-cyclisation to form the betaines 16 which, in turn, isomerise with opening of the bridging bond to give the aminopyridazines 13 . In a similar manner, the tris[amino] cyclopropenylium salts 8a,b and 10a-c are converted to the 3,4,5-tris[amino]-pyridazines ( 21a-k ) by treatment with diazomethyl compounds ( 12a, c-f ).     

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