Selective Imaging of Damaged Bone Structure (Microcracks) Using a Targeting Supramolecular Eu(III) Complex As a Lanthanide Luminescent Contrast Agent

The synthesis and photophysical evaluation of a new supramolecular lanthanide complex is described which was developed as a luminescent contrast agent for bone structure analysis. We show that the Eu(III) emission of this complex is not pH dependent within the physiological pH range, and that its steady state emission is not significantly modulated by a series of group I and II as well as d-metal ions, and that this agent can be successfully employed to image mechanically formed cracks (scratches) in bone samples after 4 or 24 hours, using confocal laser-scanning microscopy.

Lanthanide(III) nitrobenzenesulfonates as new nitration catalysts: The role of the metal and of the counterion in the catalytic efficiency

Lanthanide(III) complexes of p-nitrobenzenesulfonic acid, Ln(p-NBSA)(3), m-nitrobenzenesulfonic acid, Ln(m-NBSA)(3), and 2,4-nitrobenzenesulfonic acid, Ln(2,4-NBSA)(3), were prepared, characterized and examined as catalyst for the nitration of benzene, toluene, xylenes, naphthalene, bromobenzene and chlorobenzene. The initial screening of the catalysts showed that lanthanum(III) complexes were more effective than the corresponding ytterbium(III) complexes, and that catalysts containing the bulky 2,4-NBSA ligand were less effective than the catalyst containing p-NBSA (nosylate) or m-NBSA ligands. Examination of a series of Ln(p-NBSA)(3) and Ln(m-NBSA)(3) catalysts revealed that there is a clear correlation between the ionic radii of the lanthanide(III) ions and the yields of nitration, with the lighter lanthanides being more effective. The X-ray single crystal structure of Yb(m-NBSA)(3).6H(2)O shows that two m-NBSA ligands are directly bound to the metal centre while the third ligand is not located in the first coordination sphere, but it is hydrogen bonded to one of the water molecules which is coordinated to ytterbium(III). NMR studies suggest that this structure is preserved under the conditions used in the nitration reaction. The structure of Yb(m-NBSA)(3) is markedly different from the structure of the well-known ytterbium(III) triflate catalyst. The coordination of the nitrobenzenesulfonate counterion to the lanthanide(III) ion suggests that steric effects might play an important role in determining the efficiency of these novel nitration catalysts. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

Prognostic Significance of TRAIL Signaling Molecules in Stage II and III Colorectal Cancer

Purpose: We previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance of c-FLIP, caspase 8, TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer.

Experimental Design: Tissue microarrays were constructed from matched normal and tumor tissue derived from patients (n = 253) enrolled in a phase III trial of adjuvant 5-fluorouracil–based chemotherapy versus postoperative observation alone. TRAIL, DR5, caspase 8, and c-FLIP expression levels were determined by immunohistochemistry.

Results: Colorectal tumors displayed significantly higher expression levels of c-FLIP (P < 0.001), caspase 8 (P = 0.01), and DR5 (P < 0.001), but lower levels of TRAIL (P < 0.001) compared with matched normal tissue. In univariate analysis, higher TRAIL expression in the tumor was associated with worse overall survival (P = 0.026), with a trend to decreased relapse-free survival (RFS; P = 0.06), and higher tumor c-FLIP expression was associated with a significantly decreased RFS (P = 0.015). Using multivariate predictive modeling for RFS in all patients and including all biomarkers, age, treatment, and stage, we found that the model was significant when the mean tumor c-FLIP expression score and disease stage were included (P < 0.001). As regards overall survival, the overall model was predictive when both TRAIL expression and disease stage were included (P < 0.001).

Conclusions: High c-FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse.

Use of synthetic peptides to locate novel integrin alpha(2)beta(1)-binding motifs in human collagen III

A set of 57 synthetic peptides encompassing the entire triple-helical domain of human collagen III was used to locate binding sites for the collagen-binding integrin alpha(2)beta(1). The capacity of the peptides to support Mg2+-dependent binding of several integrin preparations was examined. Wild-type integrins (recombinant alpha(2) I-domain, alpha(2)beta(1) purified from platelet membranes, and recombinant soluble alpha(2)beta(1) expressed as an alpha(2)-Fos/beta(1)-Jun heterodimer) bound well to only three peptides, two containing GXX'GER motifs (GROGER and GMOGER, where O is hydroxyproline) and one containing two adjacent GXX'GEN motifs (GLKGEN and GLOGEN). Two mutant alpha(2) I-domains were tested: the inactive T221A mutant, which recognized no peptides, and the constitutively active E318W mutant, which bound a larger subset of peptides. Adhesion of activated human platelets to GER-containing peptides was greater than that of resting platelets, and HT1080 cells bound well to more of the peptides compared with platelets. Binding of cells and recombinant proteins was abolished by anti-alpha(2) monoclonal antibody 6F1 and by chelation of Mg2+. We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides.

OXIDATIVE DISSOLUTION OF CHROMIUM(III) OXIDES BY METAPERIODATE IONS IN PERCHLORIC-ACID

The kinetics of oxidative dissolution of a number of different samples of chromium(III) oxide by periodate ions in 1 mol dm-3 HClO4 solution have been studied and the results interpreted using the inverse-cubic rate law. The metaperiodate acts as a two-electron oxidant and the overall reaction stoichiometry involves the reaction of 3 mol of periodate with 1 mol of Cr(III) oxide. From a detailed study of the kinetics of dissolution the rate-determining step appears to be the reaction between an adsorbed periodate ion and its associated Cr(III) oxide surface site, with inhibition by one of the reaction products, iodate, through competitive adsorption. Analysis of the kinetic data generates values for the Langmuir adsorption coefficients for periodate and iodate ions on highly hydrated Cr(III) oxide of 84 +/- 8 and 2600 +/- 370 dm3 mol-1, respectively. The Cr(III) oxide-periodate reaction has a high overall activation energy, 82 +/- 6 kJ mol-1. The kinetics of dissolution of highly hydrated Cr(III) oxide under conditions in which the simple inverse-cubic rate law function does not apply can be successfully predicted using a simple kinetic model.

Presence of cave bears in western Austria before the onset of the Last Glacial Maximum: new radiocarbon dates and palaeoclimatic considerations

Tischoferhohle and Pendling-Barenhohle near Kufstein, Tyrol, are among the only locations where remains of cave bear, Ursus spelaeus-group, were found in the western part of Austria. One sample from each site was radiocarbon-dated four decades ago to ca. 28 C-14 ka BP. Here we report that attempts to date additional samples from Pendling-Barenhohle have failed due to the lack of collagen, casting doubts on the validity of the original measurement. We also unsuccessfully tried to date flowstone clasts embedded in the bone-bearing sediment to provide maximum constraints on the age of this sediment. Ten cave bear bones from Tischoferhohle showing good collagen preservation were radiocarbon-dated to 31.1-39.9 C-14 ka BP, again pointing towards an age underestimation by the original radiocarbon-dated sample from this site. These new dates from Tischoferhohle are therefore currently the only reliable cave bear dates in western Austria and constrain the interval of cave occupation to 44.3-33.5 cal ka BP. We re-calibrate and re-evaluate dates of alpine cave bear samples in the context of available palaeoclimate information from the greater alpine region covering the transition into the Last Glacial Maximum, eventually leading to the demise of this megafauna.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

Determination of the nature of the diperiodatocuprate(III) species in aqueous alkaline medium through a kinetic and mechanistic study on the oxidation of iodide ion

The nature of the diperiodatocuprate(III) (DPC) species present in aqueous alkaline medium has been investigated by a kinetic and mechanistic study on the oxidation of iodide by DPC. The reaction kinetics were studied over the 1.0 ´ 10)3±0.1 mol dm)3 alkali range. The reaction order with respect to DPC, as well as iodide, was found to be unity when [DPC] [I)]. In the 1.0 ´ 10)3±1.0 ´ 10)2 mol dm)3 alkali region, the rate decreased with increase in the alkali concentration and a plot of the pseudo-®rst order rate constant, k versus 1/[OH)] was linear. Above 5.0 ´ 10)2 mol dm)3, a plot of k versus [OH)] was also linear with a non-zero intercept. An increase in ionic strength of the reaction mixtures showed no e ect on k at low alkali concentrations, whereas at high concentrations an increase in ionic strength leads to an increase in k. A plot of 1/k versus [periodate] was linear with an intercept in both alkali ranges. Iodine was found to accelerate the reaction at the three di erent alkali concentrations employed. The observed results indicated the following equilibria for DPC.

The credit relationship between Henry III and merchants of Douai and Ypres, 1247-70

This article looks at an important but neglected aspect of medieval sovereign debt, namely ‘accounts payable’ owed by the Crown to merchants and employees. It focuses on the unusually well-documented relationship between Henry III, King of England between 1216 and 1272, and Flemish merchants from the towns of Douai and Ypres, who provided cloth on credit to the royal wardrobe. From the surviving royal documents, we reconstruct the credit advanced to the royal wardrobe by the merchants of Ypres and Douai for each year between 1247 and 1270, together with the king's repayment history. The interactions between the king and the merchants are then analysed. The insights from this analysis are applied to the historical data to explain the trading decisions made by the merchants during this period, as well as why the strategies of the Yprois sometimes differed from those of the Douaissiens.