Recent developments in X-UV optics and X-UV diagnostics

Metrology of XUV beams (X-ray lasers, high-harmonic generation and VUV free-electron lasers) is of crucial importance for the development of applications. We have thus developed several new optical systems enabling us to measure the optical properties of XUV beams. By use of a Michelson interferometer working as a Fourier-transform spectrometer, the line shapes of different X-ray lasers have been measured with a very high accuracy (Deltalambda/lambdasimilar to10(-6)). Achievement of the first XUV wavefront sensor has enabled us to measure the beam quality of laser-pumped as well as discharge-pumped X-ray lasers. A capillary discharge X-ray laser has demonstrated a very good wavefront allowing us to achieve an intensity as high as 3x10(14) W cm(-2) by focusing with a f=5 cm mirror. The sensor accuracy has been measured using a calibrated spherical wave generated by diffraction. The accuracy has been estimated to be as good as lambda/120 at 13 nm. Commercial developments are underway. At Laboratoire d'Optique Appliquee, we are setting up a new beamline based on high-harmonic generation in order to start the femtosecond, coherent XUV optic .

In vitro release of nonoxynol-9 from silicone matrix intravaginal rings

The controlled-release characteristics of matrix silicone intravaginal rings loaded with between 100 and 971 mg of nonoxynol-9 have been investigated with a view to developing a ring that may offer a new female-controlled method for the prevention of transmission of sexually transmitted diseases, particularly HIV. Intravaginal rings containing 253, 487 and 971 mg of nonoxynol-9 provided a daily release of 2 mg or more over the 8-day release period, the minimal amount of nonoxynol-9 considered to provide an effective vaginal concentration for the prevention of HIV. Furthermore, the maximum daily release of N9 was about 6 mg, an amount significantly smaller than that observed for other nonoxynol-9 products whose large daily doses may in fact increase the occurrence of HIV by causing epithelial damage to the vaginal tissue. The release mechanism of the liquid nonoxynol-9 from the intravaginal rings has also been investigated and compared to models describing the release of solid drugs from the rings. It has been demonstrated through release studies and surface microscopy that a drug depletion zone is not established in such liquid-loaded intravaginal ring systems, with implications for the release kinetics. (C) 2003 Elsevier B.V. All rights reserved.

Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. Methods One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. Results There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P

Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

AIMS/HYPOTHESIS: This study examined the biological effects of the GIP receptor antagonist, (Pro3)GIP and the GLP-1 receptor antagonist, exendin(9-39)amide.

METHODS: Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic ( ob/ ob) mice.

RESULTS: In GIP receptor-transfected fibroblasts, (Pro(3))GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%; p<0.001) from clonal BRIN-BD11 cells, but had no effect on GLP-1-stimulated insulin release. In contrast, exendin(9-39)amide inhibited both GIP and GLP-1-stimulated insulin release (57% and 44%, respectively; p<0.001). Administration of (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides (25 nmol/kg body weight, i.p.) to fasted (ob/ob) mice decreased the plasma insulin responses by 42%, 54% and 49%, respectively (p<0.01 to p<0.001). The hyperinsulinaemia of non-fasted (ob/ob) mice was decreased by 19%, 27% and 18% (p<0.05 to p<0.01) by injection of (Pro3)GIP, exendin(9-39)amide or combined peptides but accompanying changes of plasma glucose were small.

CONCLUSIONS/INTERPRETATION: These data show that (Pro(3))GIP is a specific GIP receptor antagonist. Furthermore, feeding studies in one commonly used animal model of obesity and diabetes, (ob/ob) mice, suggest that GIP is the major physiological component of the enteroinsular axis, contributing approximately 80% to incretin-induced insulin release.

On the solvation of L-aspartic acid

We use molecular statics and dynamics to study the stability of L-aspartic acid both in vacuo and solvated by polar and non-polar molecules using density functional theory in the generalized gradient approximation. We find that structures stable in vacuo are unstable in aqueous solution and vice versa. From our simulations we are able to come to some conclusions about the mechanism of stabilisation of zwitterions by polar protic solvents, water and methanol.

Triply differential single ionization cross sections in coplanar and non-coplanar geometry for fast heavy ion-atom collisions

We have performed a kinematically complete experiment and calculations on single ionization in 100 MeV/amu C6+ + He collisions. For electrons ejected into the scattering plane (defined by the initial and final projectile momentum vectors) our first- and higher-order calculations are in good agreement with the data. In the plane perpendicular to the scattering plane and containing the initial projectile axis a strong forward-backward asymmetry is observed. In this plane both the first-order and the higher-order calculations do not provide good agreement neither with the data nor amongst each other.

North European last glacial-interglacial transition (LGIT; 15-9 ka) tephrochronology: extended limits and new events

High-precision correlation of palaeoclimatic and palaeoenvironmental records is crucial for testing hypotheses of synchronous change. Although radiocarbon is the traditional method for dating late Quaternary sedimentary sequences, particularly during the last glacial–interglacial transition (LGIT; 15–9?ka), there are inherent problems with the method, particularly during periods of climate change which are often accompanied by major perturbations in atmospheric radiocarbon content. An alternative method is the use of tephras that act as time-parallel marker horizons. Within Europe, numerous volcanic centres are known to have erupted during the LGIT, providing considerable potential for high-precision correlation independent of past radiocarbon fluctuations. Here we report the first identification of the Vedde Ash and Askja Tephra in Ireland, significantly extending the known provenance of these events. We have also identified two new horizons (the Roddans Port Tephras A and B) and tentatively recognise an additional horizon from Vallensgård Mose (Denmark) that provide crucial additional chronological control for the LGIT. Two phases of the Laacher See Tephra (LST) are reported, the lower Laacher See Tephra (LLST) and probably the C2 phase of the Middle Laacher See Tephra (MLST-C2) indicating a more northeasterly distribution of this fan than reported previously.