Synthesis and Biological Evaluation of Chromium Bioorganometallics Based on the Antibiotic Platensimycin Lead Structure

The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure–activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (η⁶‐pentamethylbenzene)Cr(CO)₃ ( 2 ) and (η⁶‐benzene)Cr(CO)₃ ( 3 ), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against B. subtilis 168 (Gram positive) and E. coli W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against E. coli but derivative 2 inhibits B. subtilis growth at a moderate MIC value of 0.15 mM . To test the intrinsic toxicity of chromium, several chromium salts along with {η⁶‐(3‐pentamethylphenyl propionic acid)}Cr(CO)₃ ( 5 ) and {η⁶‐(3‐phenyl propionic acid)}Cr(CO)₃ ( 6 ) were tested against both bacterial strains. No activity was observed against E. coli for any of the compounds; B. subtilis growth was not inhibited by Cr(NO₃)₃ and only very weakly by 5 , K₂Cr₂O₇ and Na₂CrO₄ at MIC values of 0.5, 0.68 and 1.24 mM , respectively. Compounds 2 , 3 , 5 and 4 (the pure organic analogue of 2 ) show similar cytotoxicity against HeLa, HepG2 and HT‐29 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds 2 , 3 and Cr(NO₃)₃ in B. subtilis were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound 2 was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in B. subtilis.     

Stylized facts of financial time series and hidden semi-Markov models

Hidden Markov models reproduce most of the stylized facts about daily series of returns. A notable exception is the inability of the models to reproduce one ubiquitous feature of such time series, namely the slow decay in the autocorrelation function of the squared returns. It is shown that this stylized fact can be described much better by means of hidden semi-Markov models. This is illustrated by examining the fit of two such models to 18 series of daily sector returns.     

HTGR reactor physics and fuel cycle studies

The high-temperature gas-cooled reactor (HTGR) appears as a good candidate for the next generation of nuclear power plants. In the “HTR-N” project of the European Union Fifth Framework Program, analyses have been performed on a number of conceptual HTGR designs, derived from reference pebble-bed and hexagonal block-type HTGR types. It is shown that several HTGR concepts are quite promising as systems for the incineration of plutonium and possibly minor actinides.These studies were mainly concerned with the investigation and intercomparison of the plutonium and actinide burning capabilities of a number of HTGR concepts and associated fuel cycles, with emphasis on the use of civil plutonium from spent LWR uranium fuel (first generation Pu) and from spent LWR MOX fuel (second generation Pu). Besides, the “HTR-N” project also included activities concerning the validation of computational tools and the qualification of models. Indeed, it is essential that validated analytical tools are available in the European nuclear community to perform conceptual design studies, industrial calculations (reload calculations and the associated core follow), safety analyses for licensing, etc., for new fuel cycles aiming at plutonium and minor actinide (MA) incineration/transmutation without multi-reprocessing of the discharged fuel.These validation and qualification activities have been centred round the two HTGR systems currently in operation, viz. the HTR-10 and the HTTR. The re-calculation of the HTTR first criticality with a Monte Carlo neutron transport code now yields acceptable correspondence with experimental data. Also calculations by 3D diffusion theory codes yield acceptable results. Special attention, however, has to be given to the modelling of neutron streaming effects. For the HTR-10 the analyses focused on first criticality, temperature coefficients and control rod worth. Also in these studies a good correspondence between calculation and experiment is observed for the 3D diffusion theory codes.     

A comprehensive database schema integration method based on the theory of formal concepts

Integrating heterogeneous database schemata is a major task in federated database design where preexisting and heterogeneous database systems need to be integrated virtually by providing a homogenization database interface. Most proposed schema integration methods suffer from very complex result schemata and insufficient handling of extensional relations, i.e. in the way how redundant data of the input systems are dealt with. Redundancy among the input systems may thus remain undetected and, hence, remains uncontrolled.Our GIM (Generic Integration Model) method is based on the elegant and mathematically founded theory of formal concept analysis (FCA). The main idea is to integrate schemata into one formal context which is a binary relation between a set of attributes and a set of base extensions (set of potential objects). From that context we apply an FCA-algorithm to semi-automatically derive a concept lattice which we interpret as an inheritance hierarchy of classes for a homogenized schema. Thus, the integration task following our method can be supported by tools.     

Verlaufsgesteuerte Trinkwasserbrunnen als neues Fassungsorgan für die Grundwassererschließung

Curved horizontal wells have been developed in the late nineties for the purpose of in situ remediation of contaminated water. The discharge of contaminated backwater has been performed very successfully. These wells are usually designed for short time use with high precision and lower requirements on productivity in comparison to the needs of fresh water discharge from groundwater. Potable water resources are explored with highly productive and durable water wells. Classical wells are vertical and radial collector wells. Under certain hydrogeological conditions a curved horizontal well may be more efficient than classical wells. Therefore well construction and design have been accepted to meet the requirements of fresh water exploration. This paper compares the three fundamental well design principles. A quantitative analytical engineering concept is presented on a basis of the Dupuit-Thiem well equation. Especially the geometry of draw-down figures is reflected in this calculations.     

The diagnostic value of thrombopoietin level measurements in thrombocytopenia

It has been reported that blood trombopoietin (TPO) levels can discriminate between thrombocytopenia due to increased platelet destruction and decreased platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a large group of patients in detail and could confirm and amplify the above notion in detail. TPO levels were determined in plasma from 178 clinically and serologically well-defined thrombocytopenic patients: 72 patients with idiopathic autoimmune thrombocytopenia (AITP), 29 patients with secondary AITP, 5 patients with amegakaryocytic thrombocytopenia and 72 patients who suffered from various diseases (46 in whom megakaryocyte deficiency was not and 26 in whom it was expected). In addition, we measured the level of glycocalicin as a marker of total body mass of platelets. In all patients with primary AITP and secondary AITP, TPO levels were within the normal range or in some (n = 7) cases only slightly increased. The level of glycocalicin was not significantly different from that of the controls (n = 95). The patients with amegakaryocytic thrombocytopenia had strongly elevated TPO levels and significantly decreased glycocalicin levels. Similarly, among the 72 thrombocytopenic patients with various disorders, elevated TPO levels were only found in patients in whom platelet production was depressed. The mean level of glycocalicin in these patients was decreased compared to that in controls and patients with AITP, but was not as low as in patients with amegakaryocytic thrombocytopenia. In conclusion, all patients with depressed platelet production had elevated levels of circulating TPO, whereas the TPO levels in patients with an immune-mediated thrombocytopenia were mostly within the normal range. Therefore, measurement of plasma TPO levels provides valuable diagnostic information for the analysis of thrombocytopenia in general. Moreover, treatment with TPO may be an option in AITP.     

Hemolytic properties and riboflavin synthesis of Helicobacter pylori: cloning and functional characterization of the ribA gene encoding GTP-cyclohydrolase II that confers hemolytic activity to Escherichia coli

Various strains of Helicobacter pylori were able to lyse erythrocytes from sheep, horse, and human when grown on blood agar. The hemolysis did not depend on the production of the vacuolating cytotoxin VacA as demonstrated by the hemolytic behavior of an isogenic vacA-negative mutant strain. The hemolytic activity could be detected in cell-free supernatants and was not regulated by iron. To isolate genes coding for proteins involved in the destruction of erythrocytes, a plasmid-based DNA library was screened for expression of lytic activity on blood agar. This approach revealed that the H. pylori ribA gene confers hemolytic properties to Escherichia coli. The ribA gene encodes the enzyme GTP-cyclohydrolase II [EC 3.5.4.25] that catalyzes the initial step in the synthesis of riboflavin. The predicted amino acid sequence of the H. pylori RibA protein showed a high degree of similarity to equivalent enzymes from microorganisms and from plants. The single gene on a plasmid restored riboflavin synthesis in a ribA mutant of E. coli and induced hemolytic activity. Furthermore, ribA overexpression was associated with the production of a fluorescent yellow molecule that was not identical with riboflavin. Hemolysis was also seen for the ribA gene from E. coli, indicating that this feature was not specific for the H. pylori gene. The presence of ribA in various H. pylori strains was confirmed by Southern blot hybridization and by polymerase chain reaction with specific primers. This analysis revealed that microdiversity exists within the DNA region upstream from ribA, which was further confirmed by nucleotide sequence analysis.     

Kinetic study on the alkaline degradation of cotton hydrocellulose

The kinetics of alkaline degradation of cotton hydrocellulose were determined in 5% NaOH at various temperatures. An activation energy of 24 kcal./mole was found for the endwise degradation reaction, while that of termination to a stable m-saccharinic acid endunit is 32 kcal./mole. Consequently, the DP_n of the degradable chain length is highly dependent on the reaction temperature, being 1000 at 65°C. and 140 at 132°C. At lower temperatures, the majority of degrading chains terminate to a normal reducing endgroup at the crystalline–amorphous transition region. From the data, the D P_n of cellulose chain segments participating in the amorphous regions of the original cotton fibril was calculated to be 143. This result strongly supports the classical micellar fibril structure over the folded model proposed by Manley.     

Lymphography in testicular tumors (author's transl)

Results of lymphography in 101 cases of testicular tumor are described. Secondaries could be shown in 43% of seminomas and 46% of teratomas. Examples show the criteria of lymphographic diagnosis of secondaries. Lymphography permits a) more exact classification of stages b) better planning and control of treatment and c) prognosis.     

Silicon doping by nuclear transmutation

This paper describes, from the view of nuclear physics and radiochemistry, the mode of operation in doping semiconductor silicon with phosphorus by neutron irradiation. In addition to precise control of the irradiation fluence, this includes control of neutron-flux distribution, self-shielding and radioactive products from the silicon matrix and the surface impurities. The accuracy of the resistivity values achieved by this method is better than ± 5% at the predicated value. The good homogeneity of the dopant distribution is shown by the results of location-resolving resistivity measurements as well as by the breakdown radiation emitted by diodes. Neutron-bombarded homogeneously doped silicon (NBH-silicon) is used for routine manufacture of multi-diode vidicons and power devices.