Mitochondrial Functions are Major Targets of Isocyanide Activity in \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e

The isocyanide functional group is important in the synthesis of many organic compounds and is found in natural products produced by plants, bacteria, marine invertebrates, and fungi. The antimicrobial activities of isocyanide compounds have been documented for almost 70 years, however, the biochemical targets and mechanisms of action remain poorly defined. We report antimicrobial activity of 4-para-nitrophenyl-isocyanide (p-NPIC) against a model fungus, Saccharomyces cerevisiae, and the human fungal pathogen Candida albicans. To identify the cellular and molecular targets of p-NPIC, we screened the non-essential single gene-deletion collection of S. cerevisiae. We aimed to identify genes which, when absent, rendered the resulting strain incapable of growth on solid media containing 1.5 µM p-NPIC. We identified 167 strains that were hypersensitive to p-NPIC and determined the minimum inhibitory concentration of p-NPIC for each of these mutant strains. The most sensitive deletion-strains (MIC \u3c 3.0 µM in liquid media) were enriched in mitochondrial functions including the mitochondrial type II fatty acid synthase, lipoic acid biosynthesis and protein lipoylation, synthesis and assembly of iron-sulfur clusters, and assembly and maintenance of cytochrome c oxidase. The identification of essentially all components of the proton-pumping vacuolar membrane ATPase, as well as some pH sensitive components of membrane lipid biosynthesis, also suggest a role for regulation of cytoplasmic pH as a key determinant of p-NPIC tolerance. Taken together, these results suggest that mitochondrial metal homeostasis and reactive oxygen scavenging are disrupted by p-NPIC treatment and provide new information about the potential mechanisms of action of isocyanide natural products. Advisor: Wayne R. Riekho

Virtual labs in Leonardo da Vinci

This paper discusses the problem of virtual lab capabilities in the e-learning. Using combination of web conferencing and "virtual labs" capabilities, a new quality distance learning teaching is now in preparation and will be included in the course teaching to produce interactive, online simulations for the natural gas engineering studies. The activities are designed to enhance the existing curriculum and to include online assessments. A special care is devoted to the security problem between a server and a client computer. Several examples of the virtual labs related to the PVT thermodynamics, fluid flow, the natural gas well-testing, and thev gas network flow are prepared and tested. A major challenge for the 'CELGAS' system is in managing the delicate balance between the student collaboration and the isolation. Students may be encouraged to collaborate and work with each other, simulating their exploration of the lab material

Characteristics of the annihilation of positrons in nanosized metal coatings Zr/Nb

New technologies for producing structural materials that are resistant to hydrogen and radiation damage are pressing problems in materials science. Hydrogen damage and radiation degradation are important factors limiting the fatigue life of structural materials. One promising alternative in developing radiation-hydrogen-resistant materials with improved physical and mechanical properties is the application of nanoscale metal coatings (NMC). The current work is devoted to studying positron annihilation in NMC Zr/Nb with different thicknesses of individual layers, Zr and Nb

Demokratie und Philosophie : Die Antike und das politische Ethos des europäischen Denkens

Die von Richard Rorty unlängst aufgestellte These über die „Priorität der Demokratie vor Philosophie“ erregte zwar manche Bedenken und Zweifel, aber die darin implizierte Frage nach dem politischen Ethos des modernen europäischen Denkens gewinnt heute offensichtlich eine neue Aktualität. Unter vielen Dimensionen und Aspekten dieser Neubesinnung der modernen Vernunft auf ihre eigene Verschränkung mit der Politik gibt es auch nicht zuletzt solche, die sich auf geschichtliche Ursprünge und Wurzeln der europäischen Kultur beziehen, deren wichtigste die geistige und gesellschaftliche Welt der griechischen Antike bildet. Denn dort und damals entstehen die beiden, die Philosophie ebenso wie die Demokratie, und zwar gleichzeitig. Nun wollen wir diesen Zusammenhang der gemeinsamen Geburt am gleichen Ort und in gleicher Zeit, der zwischen dem philosophischen logos des europäischen Denkens und dem demokratischen Ethos der griechischen polis offenkundig besteht, etwas näher betrachten. Ohne über den „Vorrang“ irgendwelcher von den beiden zu entscheiden, versuchen wir die Philosophie und die Demokratie in ihrem Geschwisterbund der gemeinsamen Herkunft und der gegenseitigen Zusammengehörigkeit kurz darzustellen

Characteristics of the annihilation of positrons in nanosized metal coatings Zr/Nb

New technologies for producing structural materials that are resistant to hydrogen and radiation damage are pressing problems in materials science. Hydrogen damage and radiation degradation are important factors limiting the fatigue life of structural materials. One promising alternative in developing radiation-hydrogen-resistant materials with improved physical and mechanical properties is the application of nanoscale metal coatings (NMC). The current work is devoted to studying positron annihilation in NMC Zr/Nb with different thicknesses of individual layers, Zr and Nb

Effect of Proton Irradiation on the Defect Evolution of Zr/Nb Nanoscale Multilayers

Nanoscale multilayer coatings (NMCs) with different crystal structures are considered as capable of self-healing after radiation damage due to the recombination of vacancies and interstitials. This work is focused on a defect distribution study of NMCs based on Zr/Nb layers (25/25 nm and 100/100 nm) after proton irradiation. Coatings with a total thickness of 1.05 ± 0.05 µm were irradiated by 900-keV protons using a pelletron-type electrostatic accelerator with an ion current of 2 µA for durations of 60 min to 120 min. The influence of the irradiation effect was studied by X-ray diffraction analysis (XRD), glow discharge optical emission spectrometry (GD–OES), and Doppler broadening spectroscopy using a variable energy positron beam. The results obtained by these methods are compatible and indicate that defect concentration of Zr/Nb NMCs remains unchanged or slightly decreases with increasing irradiation time

Effect of Proton Irradiation on the Defect Evolution of Zr/Nb Nanoscale Multilayers

Nanoscale multilayer coatings (NMCs) with different crystal structures are considered as capable of self-healing after radiation damage due to the recombination of vacancies and interstitials. This work is focused on a defect distribution study of NMCs based on Zr/Nb layers (25/25 nm and 100/100 nm) after proton irradiation. Coatings with a total thickness of 1.05 ± 0.05 µm were irradiated by 900-keV protons using a pelletron-type electrostatic accelerator with an ion current of 2 µA for durations of 60 min to 120 min. The influence of the irradiation effect was studied by X-ray diffraction analysis (XRD), glow discharge optical emission spectrometry (GD–OES), and Doppler broadening spectroscopy using a variable energy positron beam. The results obtained by these methods are compatible and indicate that defect concentration of Zr/Nb NMCs remains unchanged or slightly decreases with increasing irradiation time

Demokratie und Philosophie: Die Antike und das politische Ethos des europäischen Denkens = Democracy and Philosophy: Antiquity and the Political Ethos of European Thought. ZEI Discussion Papers: 1999, C 46

[Introduction]. Die von Richard Rorty unlängst aufgestellte These über die "Priorität der Demokratie vor Philosophie" erregte zwar manche Bedenken und Zweifel, aber die darin implizierte Frage nach dem politischen Ethos des modernen europäischen Denkens gewinnt heute offensichtlich eine neue Aktualität. Unter vielen Dimensionen und Aspekten dieser Neubesinnung der modernen Vernunft auf ihre eigene Verschränkung mit der Politik gibt es auch nicht zuletzt solche, die sich auf geschichtliche Ursprünge und Wurzeln der europäischen Kultur beziehen, deren wichtigste die geistige und gesellschaftliche Welt der griechischen Antike bildet. Denn dort und damals entstehen die beiden, die Philosophie ebenso wie die Demokratie, und zwar gleichzeitig. Nun wollen wir diesen Zusammenhang der gemeinsamen Geburt am gleichen Ort und in gleicher Zeit, der zwischen dem philosophischen logos des europäischen Denkens und dem demokratischen Ethos der griechischen polis offenkundig besteht, etwas näher betrachten. Ohne über den „Vorrang“ irgendwelcher von den beiden zu entscheiden, versuchen wir die Philosophie und die Demokratie in ihrem Geschwisterbund der gemeinsamen Herkunft und der gegenseitigen Zusammengehörigkeit kurz darzustellen