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101.
Griebenow N Buchmueller A Kolkhof P Schamberger J Bischoff H 《Bioorganic & medicinal chemistry letters》2011,21(12):3648-3653
Novel squalene synthase inhibitors are disclosed. The design, synthesis, SAR and pharmacological profile of the compounds are discussed. 相似文献
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AIMS: The dynamics of bioaerosol generation in specific occupational environments where mail is manually unpacked and sorted was investigated. METHODS AND RESULTS: Total number of airborne particles was determined in four different size classes (0.3-0.5, 0.5-1, 1-5 and >5 microm) by laser particle counting. Time dependent formation of bioaerosols was monitored by culturing methods and by specific staining followed by flow cytometry. Besides handling of regular mail, specially prepared letters ('spiked letters') were added to the mailbags to deliberately release powdered materials from letters and to simulate high impact loads. These letters contained various dry powdered biological and nonbiological materials such as milk powder, mushrooms, herbs and cat litter. Regarding the four size classes, particulate aerosol composition before mail handling was determined as 83.2 +/- 1.0, 15.2 +/- 0.7, 1.7 +/- 0.4 and 0.04 +/- 0.02%, respectively, whereas the composition changed during sorting to 66.8 +/- 7.9, 22.3 +/- 3.6, 10.4 +/- 4.0 and 0.57 +/- 0.27%, respectively. Mail processing resulted in an increase in culturable airborne bacteria and fungi. Maximum concentrations of bacteria reached 450 CFU m(-3), whereas 270 CFU of fungi were detected. CONCLUSIONS: Indoor particle concentrations steadily increased during mail handling mostly associated with particles of diameters >1 microm. However, it was not possible to distinguish spiked letters from nonspiked by simple particle counting and CFU determinations. SIGNIFICANCE AND IMPACT OF STUDY: The dynamics of bioaerosol generation have to be addressed when monitoring specific occupational environments (such as mail sorting facilities) regarding the occurrence of biological particles. 相似文献
105.
Misof B Niehuis O Bischoff I Rickert A Erpenbeck D Staniczek A 《Journal of experimental zoology. Part B. Molecular and developmental evolution》2006,306(1):70-88
RNA molecules and in particular the nuclear SSU RNA play an important role in molecular systematics. With the advent of increasingly parameterized substitution models in systematic research, the incorporation of secondary-structure information became a realistic option compensating interdependence of character variation. As a prerequisite, consensus structures of eukaryotic SSU RNA molecules have become available through extensive comparative analyses and crystallographic studies. Despite extensive research in hexapod phylogenetics, consensus SSU RNA secondary structures focusing on hexapods have not yet been explored. In this study, we compiled a representative hexapod SSU data set of 261 sequences and inferred a specific consensus SSU secondary-structure model. Our search for conserved structural motives relied on a combined approach of thermodynamic and covariation analyses. The hexapod consensus-structure model deviates from the canonical eukaryotic model in a number of helices. Additionally, in several helices the hexapod sequences did not support a single consensus structure. We provide consensus structures of these sections of single less-inclusive taxa, thus facilitating the adaptation of the consensus hexapod model to less-inclusive phylogenetic questions. The secondary-structure catalog will foster the application of RNA structure models in phylogenetic analyses using the SSU rRNA molecule, and it will improve the realism of substitution models and the reliability of reconstructions based on rRNA sequences. 相似文献
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Bischoff JE 《Journal of biomechanics》2006,39(7):1361-2; author reply1362
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Stephen R Hughes Steven B Riedmuller Jeffrey A Mertens Xin-Liang Li Kenneth M Bischoff Nasib Qureshi Michael A Cotta Philip J Farrelly 《Proteome science》2006,4(1):10-14
Background
The field of plasmid-based functional proteomics requires the rapid assay of proteins expressed from plasmid libraries. Automation is essential since large sets of mutant open reading frames are being cloned for evaluation. To date no integrated automated platform is available to carry out the entire process including production of plasmid libraries, expression of cloned genes, and functional testing of expressed proteins. 相似文献109.
Martínez González S Hernández AI Varela C Rodríguez-Arístegui S Lorenzo M Rodríguez A Rivero V Martín JI Saluste CG Ramos-Lima F Cendón E Cebrián D Aguirre E Gomez-Casero E Albarrán M Alfonso P García-Serelde B Oyarzabal J Rabal O Mulero F Gonzalez-Granda T Link W Fominaya J Barbacid M Bischoff JR Pizcueta P Pastor J 《Bioorganic & medicinal chemistry letters》2012,22(10):3460-3466
Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein, we describe the optimization of imidazo [1,2-a] pyrazines, which allow us to identify compound 14 (ETP-46321), with potent biochemical and cellular activity and good pharmacokinetic properties (PK) after oral dosing. ETP-46321 PK/PD studies showed time dependent downregulation of AKT(Ser473) phosphorylation, which correlates with compound levels in tumor tissue and demonstrating to be efficacious in a GEMM mouse tumor model driven by a K-Ras(G12V) oncogenic mutation. Treatment with ETP-46321 resulted in significant tumor growth inhibition. 相似文献
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Poole TL Callaway TR Bischoff KM Loneragan GH Anderson RC Nisbet DJ 《Journal of applied microbiology》2012,113(3):659-668