Serial defaults, serial profits: Returns to sovereign lending in Habsburg Spain, 1566-1600

Philip II of Spain accumulated debts equivalent to 60% of GDP. He also defaulted four times onhis short-term loans, thus becoming the first serial defaulter in history. Contrary to a commonview in the literature, we show that lending to the king was profitable even under worst-casescenario assumptions. Lenders maintained long-term relationships with the crown. Lossessustained during defaults were more than compensated by profits in normal times. Defaultswere not catastrophic events. In effect, short-term lending acted as an insurance mechanism,allowing the king to reduce his payments in harsh times in exchange for paying a premium intranquil periods. © 2010 Elsevier Inc. All rights reserved.

In vivo characterization of sunitinib eluting beads

Purpose: To study the pharmacokinetics and potential toxicity of sunitinib eluting beads in an animal modelMaterials: Healthy New-Zealand white rabbits were used. 8 animals received 0.2ml of DC Beads loaded with 6mg of sunitinb intra arterially in the hepatic artery (group 1) and 4 animals received 6mg of sunitinib administered orally (group 2). In group 1, animals were sacrificed 6 hours (n=4) and 24 hours (n=4) after embolization. In group 2, animals were sacrificed 6 hours (n=2) and 24 hours (n=2) after oral administration of sunitinib. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was measured by LC MS/MS tandem mass spectroscopy at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS tandem mass spectroscopy.Results: After embolization we observed an expected elevation of AST and ALT. Serial plasmatic measurments after embolization showed a very low sunitinib concentration (<50ng/ml). Measurment of sunitinib in the embolized liver tissue showed a very high concentration at 6 hours (3870ng/ml) and 24 hours (4741.7ng/ml).Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered intra-arterially in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration canbe obtained at the site of embolization with minimal systemic passage.

La secuencia onírica y la construcción de la interioridad en la ficción serial contemporánea.

El presente trabajo trata sobre el imaginario de la interioridad en el contexto de la ficción serial contemporánea. Sin establecer una ruta definida por una variable formal determinada (autor, género, corriente estilísitca, etc.) enfocaré este estudio en el recurso expresivo de la secuencia onírica, entendiendo por tal no sólo la filmación de escenas pertenecientes al ámbito del sueño sino también a la recreación del delirio, la alucinación, las visiones, etc.En un sentido amplio, dada la naturaleza del tema escogido, se hará necesaria una reflexión sobre la relación entre vigilia, sueño, tiempo e identidad, así como una reflexión sobre el modo en que la redefinición de estos conceptos desencadena paralelamente una nueva relación de los componentes narrativos con el relato mismo.

Détail pour les distances qu'il y a d'un col ou d'un poste à un autre en lignes horizontalle et le tems qu'il faut pour aller d'un passage à l'autre d'un pas reglé

Ancien possesseur : Argenson, Antoine-René de Voyer (1722-1787 ; marquis de Paulmy d')

Serial protein labeling with infrared maleimide dyes to identify cysteine modifications

Cysteine thiol modifications are increasingly recognized to occur under both physiological and pathophysiological conditions, making their accurate detection, identification and quantification of growing importance. However, saturation labeling of thiols with fluorescent dyes results in poor protein recuperation and therefore requires the use of large quantities of starting material. This is especially important in sequential dye-labeling steps when applied for an identification of cysteine modifications. First, we studied the effects of different detergents during labeling procedure, i.e. Tween 20, Triton X-100 and CHAPS, on protein yield and composition. Tween 20 and Triton X-100 resulted in yields of around 50% labeled proteins compared to only 10% with PBS alone and a most diversified 2-DE protein pattern. Secondly, Tween 20 was used for serial protein labeling with maleimid fluorophores, first to conjugate to accessible thiols and after a reduction to label with another fluorophore previously masked di-sulphide and/or oxidized proteins in frontal cortex autopsy tissue of a subject with mild Alzheimer's disease. Two-DE DIGE revealed a complex protein pattern of readily labeled thiols and di-sulphide and/or oxidized proteins. Seventeen proteins were identified by MALDI-TOF and by peptide fingerprints. Several proteins were oxidized and involved in Alzheimer's disease. However methionine oxidation was prevalent. Infrared DIGE may provide an additional tool for an identification of oxidation susceptible proteins.