The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Beschreibung der vorzüglichsten Merkwürdigkeiten und Kunstsachen der Stadt Magdeburg aus den alten und neuern Zeiten

auf Kosten des Domküsters Johann Friedrich Eberhard Burgmüller. [August Christoph Meinecke]Autopsie nach Ex. der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Magdeburg, 1795. Gedruckt in der Güntherschen Hofbuchdruckerey

Ultra-Short Pulse Generation in a Three Section Tapered Passively Mode-Locked Quantum-Dot Semiconductor Laser

Abstract We experimentally and theoretically investigate the pulsed emission dynamics of a three section tapered semiconductor quantum dot laser. The laser output is characterized in terms of peak power, pulse width, timing jitter and amplitude stability and a range of outstanding pulse performance is found. A cascade of dynamic operating regimes is identified and comprehensively investigated. We propose a microscopically motivated traveling-wave model, which optimizes the computation time and naturally allows insights into the internal carrier dynamics. The model excellently reproduces the measured results and is further used to study the pulse-generation mechanism as well as the influence of the geometric design on the pulsed emission. We identify a pulse shortening mechanism responsible for the device performance, that is unique to the device geometry and configuration. The results may serve as future guidelines for the design of monolithic high-power passively mode-locked quantum dot semiconductor lasers

Hemin and Magnesium-Protoporphyrin IX Induce Global Changes in Gene Expression in Chlamydomonas reinhardtii[C][W]

Retrograde signaling is a pathway of communication from mitochondria and plastids to the nucleus in the context of cell differentiation, development, and stress response. In Chlamydomonas reinhardtii, the tetrapyrroles magnesium-protoporphyrin IX and heme are only synthesized within the chloroplast, and they have been implicated in the retrograde control of nuclear gene expression in this unicellular green alga. Feeding the two tetrapyrroles to Chlamydomonas cultures was previously shown to transiently induce five nuclear genes, three of which encode the heat shock proteins HSP70A, HSP70B, and HSP70E. In contrast, controversial results exist on the possible role of magnesium-protoporphyrin IX in the repression of genes for light-harvesting proteins in higher plants, raising the question of how important this mode of regulation is. Here, we used genome-wide transcriptional profiling to measure the global impact of these tetrapyrroles on gene regulation and the scope of the response. We identified almost 1,000 genes whose expression level changed transiently but significantly. Among them were only a few genes for photosynthetic proteins but several encoding enzymes of the tricarboxylic acid cycle, heme-binding proteins, stress-response proteins, as well as proteins involved in protein folding and degradation. More than 50% of the latter class of genes was also regulated by heat shock. The observed drastic fold changes at the RNA level did not correlate with similar changes in protein concentrations under the tested experimental conditions. Phylogenetic profiling revealed that genes of putative endosymbiontic origin are not overrepresented among the responding genes. This and the transient nature of changes in gene expression suggest a signaling role of both tetrapyrroles as secondary messengers for adaptive responses affecting the entire cell and not only organellar proteins