The 5.25 & 5.7 μ\mum Astronomical Polycyclic Aromatic Hydrocarbon Emission Features

Astronomical mid-IR spectra show two minor PAH features at 5.25 and 5.7 $\mu$m (1905 and 1754 cm$^{\rm - 1}$) that hitherto have been little studied, but contain information about the astronomical PAH population that complements that of the major emission bands. Here we report a study involving both laboratory and theoretical analysis of the fundamentals of PAH spectroscopy that produce features in this region and use these to analyze the astronomical spectra. The ISO SWS spectra of fifteen objects showing these PAH features were considered for this study, of which four have sufficient S/N between 5 and 6 $\mu$m to allow for an in-depth analysis. All four astronomical spectra show similar peak positions and profiles. The 5.25 $\mu$m feature is peaked and asymmetric, while the 5.7 $\mu$m feature is broader and flatter. Detailed analysis of the laboratory spectra and quantum chemical calculations show that the astronomical 5.25 and 5.7 $\mu$m bands are a blend of combination, difference and overtone bands primarily involving CH stretching and CH in-plane and CH out-of-plane bending fundamental vibrations. The experimental and computational spectra show that, of all the hydrogen adjacency classes possible on PAHs, solo and duo hydrogens consistently produce prominent bands at the observed positions whereas quartet hydrogens do not. In all, this a study supports the picture that astronomical PAHs are large with compact, regular structures. From the coupling with primarily strong CH out-of-plane bending modes one might surmise that the 5.25 and 5.7 $\mu$m bands track the neutral PAH population. However, theory suggests the role of charge in these astronomical bands might also be important.Comment: Accepted ApJ, 40 pages in pre-print, 14 figures, two onlin

Microsieves for the detection of circulating tumor cells in leukapheresis product in non-small cell lung cancer patients

Background: Circulating tumor cells (CTC) in non-small cell lung cancer (NSCLC) patients are a prognostic and possible therapeutic marker, but have a low frequency of appearance. Diagnostic leukapheresis (DLA) concentrates CTC and mononuclear cells from the blood. We evaluated a protocol using two VyCAP microsieves to filter DLA product of NSCLC patients and enumerate CTC, compared with CellSearch as a gold standard. Methods: DLA was performed in NSCLC patients before starting treatment. DLA product equaling 2×108 leukocytes was diluted to 9 mL with CellSearch dilution buffer in a Transfix CTC tube. Within 72 hours the sample was filtered with a 7 μm pore microsieve and subsequently over a 5μm pore microsieve. CTC were defined as nucleated cells which stained for cytokeratin, but lacked CD45 and CD16. CellSearch detected CTC in the same volume of DLA. Results: Of 29 patients a median of 1.4 mL DLA product (range, 0.5-4.1) was filtered (2% of total product) successfully in 93% and 45% of patients using 7 and 5 μm pores, respectively. Two DLA products were unevaluable for CTC detection. Clogging of the 5 μm but not 7 μm microsieves was positively correlated with fixation time (ρ=0.51, P<0.01). VyCAP detected CTC in 44% (12/27) of DLA products. Median CTC count per mL DLA was 0 [interquartile range (IQR): 0-1]. CellSearch detected CTC in 63% of DLA products (median =0.9 CTC per mL DLA, IQR: 0-2.1). CTC counts detected by CellSearch were significantly higher compared with VyCAP (P=0.05). Conclusions: VyCAP microsieves can identify CTC in DLA product, but workflows need to be optimized

Spectroscopic Evidence for an Oxazolone Structure in Anionic b-Type Peptide Fragments

Infrared spectra of anionic b-type fragments generated by collision induced dissociation (CID) from deprotonated peptides are reported. Spectra of the b2 fragments of deprotonated AlaAlaAla and AlaTyrAla have been recorded over the 800–1800 cm–1 spectral range by multiple-photon dissociation (MPD) spectroscopy using an FTICR mass spectrometer in combination with the free electron laser FELIX. Structural characterization of the b-type fragments is accomplished by comparison with density functional theory calculated spectra at the B3LYP/6-31++G(d,p) level for different isomeric structures. Although diketopiperazine structures represent the energetically lowest isomers, the IR spectra suggest an oxazolone structure for the b2 fragments of both peptides. Deprotonation is shown to occur on the oxazolone α-carbon, which leads to a conjugated structure in which the negative charge is practically delocalized over the entire oxazolone ring, providing enhanced gas-phase stability

Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study

Treatment decisions after diagnosis of clinically localised prostate cancer are difficult due to variability in tumour behaviour. We therefore examined one of the most promising biomarkers in prostate cancer, Ki-67, in a cohort of 808 patients diagnosed with prostate cancer between 1990 and 1996 and treated conservatively. Ki-67 expression was assessed immunohistochemically, in two laboratories, by two different scoring methods and the results compared with cancer-specific and overall survival. The power of the biomarker was compared with Gleason score and initial serum prostate-specific antigen (PSA). Both methods showed that Ki-67 provided additional prognostic information beyond that available from Gleason score and PSA: for the semi-quantitative method, Δχ2 (1 d.f.)=24.6 (P<0.0001), overall survival χ2=20.5 (P<0.0001), and for the quantitative method, Δχ2 (1 d.f.)=15.1 (P=0.0001), overall survival χ2=10.85 (P=0.001). Ki-67 is a powerful biomarker in localised prostate cancer and adds to a model predicting the need for radical or conservative therapy. As it is already in widespread use in routine pathology, it is confirmed as the most promising biomarker to be applied into routine practice