From hexaoxy-[6]pericyclynes to carbo-cyclohexadienes, carbo-benzenes, and dihydro-carbo-benzenes: synthesis, structure, and chromophoric and redox properties.

When targeting the quadrupolar p-dianisyltetraphenyl-carbo-benzene by reductive treatment of a hexaoxy-[6]pericyclyne precursor 3 with SnCl(2)/HCl, a strict control of the conditions allowed for the isolation of three C(18)-macrocyclic products: the targeted aromatic carbo-benzene 1, a sub-reduced non-aromatic carbo-cyclohexadiene 4A, and an over-reduced aromatic dihydro-carbo-benzene 5A. Each of them was fully characterized by its absorption and NMR spectra, which were interpreted by comparison with calculated spectra from static structures optimized at the DFT level. According to the nucleus-independent chemical shift (NICS) value (NICS≈-13 ppm), the macrocyclic aromaticity of 5A is indicated to be equivalent to that of 1. This is confirmed by the strong NMR spectroscopic deshielding of the ortho-CH protons of the aryl substituents, but also by the strong shielding of the internal proton of the endocyclic trans-CH=CH double bond that results from the hydrogenation of one of the C≡C bonds of 3. Both the aromatics 1 and 5A exhibit a high crystallinity, revealed by SEM and TEM images, which allowed for a structural determination by using an X-ray microsource. A good agreement with calculated molecular structures was found, and columnar assemblies of the C(18) macrocycles were evidenced in the crystal packing. The non-aromatic carbo-cyclohexadiene 4A is shown to be an intermediate in the formation of 1 from 3. It exhibits a remarkable dichromism in solution, which is related to the occurrence of two intense bands in the visible region of its UV/Vis spectrum. These properties could be attributed to the dibutatrienylacetylene (DBA) unit that occurs in the three chromophores, but which is not involved in a macrocyclic π-delocalization in 4A only. A versatile redox behavior of the carbo-chromophores is evidenced by cyclic voltammetry and was analyzed by calculation of the ionization potential, electron affinity, and frontier molecular orbitals.

Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells.

BACKGROUND: Single Base Substitutions (SBS) that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. METHODS: We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE) and Tag-seq (a combination of L-SAGE and deep sequencing), and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT), i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. RESULTS: In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP), catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST), i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC), healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. CONCLUSION: If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient's tumor and aid diagnostic.

Inter- and intraobserver reliability of the clock face representation as used to describe the femoral intercondylar notch.

PURPOSE: To validate the use of the clock face reference as a reliable means of communicating femoral intercondylar notch position. METHODS: A single red mark was made on ten identical left Sawbones femurs in the intercondylar notch at variable locations. Ten surgeons, who routinely perform ACL reconstructions, were presented the femurs in random order and asked to state the position of the mark to the nearest 30-min interval. Responses were recorded and then repeated 3 weeks later. The same 10 surgeons were presented with 30 actual arthroscopic photographs of the intercondylar notch, performed at 90° of knee flexion, with a probe pointing at various locations (10 knees; 3 photographs/knee) along the lateral aspect of the notch. The results were then analyzed with an ICC, Cronbach's alpha test, and descriptive statistics. RESULTS: For the Sawbones, the ICC was 0.996 while individual physician's Cronbach's alpha test ranged from 0.954 to 0.999, indicating a very high interobserver and intraobserver reliability. The mean range of responses among the 10 surgeons was 1.6 h, SD 0.6. For the photographs, the ICC was also high at 0.997. There was a mean range of 1.1 h, SD 0.4, among surgeons. CONCLUSIONS: The clock face method is commonly utilized for both placement of the femoral tunnel during ACL reconstruction as well as describing the location of the ACL femoral tunnel between communicating surgeons. Despite a high statistical interobserver correlation, there is significant range among different surgeons' responses. The present study questions the reliability of the clock face method for use between surgeons as a stand alone tool. Other methods also utilizing anatomic landmarks may be more accurate for describing intercondylar notch anatomy. LEVEL OF EVIDENCE: III.

RReportGenerator: automatic reports from routine statistical analysis using R.

UNLABELLED: With the establishment of high-throughput (HT) screening methods there is an increasing need for automatic analysis methods. Here we present RReportGenerator, a user-friendly portal for automatic routine analysis using the statistical platform R and Bioconductor. RReportGenerator is designed to analyze data using predefined analysis scenarios via a graphical user interface (GUI). A report in pdf format combining text, figures and tables is automatically generated and results may be exported. To demonstrate suitable analysis tasks we provide direct web access to a collection of analysis scenarios for summarizing data from transfected cell arrays (TCA), segmentation of CGH data, and microarray quality control and normalization. AVAILABILITY: RReportGenerator, a user manual and a collection of analysis scenarios are available under a GNU public license on http://www-bio3d-igbmc.u-strasbg.fr/~wraff