Electrochemically Generated Acid and Its Containment to 100 Micron Reaction Areas for the Production of DNA Microarrays

An addressable electrode array was used for the production of acid at sufficient concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group from an overlaying substrate bound to a porous reaction layer. Containment of the generated acid to an active electrode of 100 micron diameter was achieved by the presence of an organic base. This procedure was then used for the production of a DNA array, in which synthesis was directed by the electrochemical removal of the DMT group during synthesis. The product array was found to have a detection sensitivity to as low as 0.5 pM DNA in a complex background sample

Goethes dramatische und epische Hauptwerke / kurz erläutert und beurtheilt von Carl Hoheisel, Oberlehrer

GOETHES DRAMATISCHE UND EPISCHE HAUPTWERKE / KURZ ERLÄUTERT UND BEURTHEILT VON CARL HOHEISEL, OBERLEHRER Goethes dramatische und epische Hauptwerke / kurz erläutert und beurtheilt von Carl Hoheisel, Oberlehrer (1) Einband (1) Titelseite (4) Druckvermerk (5) Vorwort (6) Inhalt (8) Einleitung (9) I. Götz von Berlichingen (18) II. Leiden des jungen Werthers (29) III. Clavigo (48) IV. Iphigenie in Tauris (63) V. Egmont (78) VI. Torquato Tasso (90) VII. Wilhelm Meisters Lehrjahre (115) VIII. Hermann und Dorothea (129) IX. Die natürliche Tochter (149) X. Wahlverwandtschaften (156) XI. Faust (179

Atteintes à la propriété, juste équilibre et compensations dans le système des droits de l'homme

BACKGROUND. Solid tumors, including head and neck squamous cell carcinomas (HNSCC), arise as a result of genetic and epigenetic alterations in a sustained stress environment. Little work has been done that simultaneously examines the spectrum of both types of changes in human tumors on a genome-wide scale and results so far have been limited and mixed. Since it has been hypothesized that epigenetic alterations may act by providing the second carcinogenic hit in gene silencing, we sought to identify genome-wide DNA copy number alterations and CpG dinucleotide methylation events and examine the global/local relationships between these types of alterations in HNSCC. METHODOLOGY/PRINCIPAL FINDINGS. We have extended a prior analysis of 1,413 cancer-associated loci for epigenetic changes in HNSCC by integrating DNA copy number alterations, measured at 500,000 polymorphic loci, in a case series of 19 primary HNSCC tumors. We have previously demonstrated that local copy number does not bias methylation measurements in this array platform. Importantly, we found that the global pattern of copy number alterations in these tumors was significantly associated with tumor methylation profiles (p<0.002). However at the local level, gene promoter regions did not exhibit a correlation between copy number and methylation (lowest q=0.3), and the spectrum of genes affected by each type of alteration was unique. CONCLUSION/SIGNIFICANCE. This work, using a novel and robust statistical approach demonstrates that, although a "second hit" mechanism is not likely the predominant mode of action for epigenetic dysregulation in cancer, the patterns of methylation events are associated with the patterns of allele loss. Our work further highlights the utility of integrative genomics approaches in exploring the driving somatic alterations in solid tumors.Flight Attendant Medical Research Institute; National Institutes of Health (5R01CA078609-10, 2R01CA100679-06A1, 5RO1ES006717-13