Metabolic and structural properties of human obestatin {1-23} and two fragment peptides

Obestatin is a peptide produced in the oxyntic mucosa of the stomach and co-localizes with ghrelin on the periphery of pancreatic islets. Several studies demonstrate that obestatin reduces food and water intake, decreases body weight gain, inhibits gastrointestinal motility, and modulates glucose-induced insulin secretion. In this study we evaluated the acute metabolic effects of human obestatin {1-23} and fragment peptides {1-10} or {11-23} in high-fat fed mice, and then investigated their solution structure by NMR spectroscopy and molecular modelling. Obestatins {1-23} and {11-23} significantly reduced food intake (86% and 90% respectively) and lowered glucose responses to feeding, whilst leaving insulin responses unchanged. No metabolic changes could be detected following the administration of obestatin (1-10). In aqueous solution none of the obestatin peptides possessed secondary structural features. However, in a 2,2,2-trifluoroethanol (TFE-d(3))-H2O solvent mixture, the structure of obestatin {1-23} was characterized by an a-helix followed by a single turn helix conformation between residues Pro(4) and Gln(15) and His(19) and Ala(22) respectively. Obestatin {1-10} showed no structural components whereas {11-23} contained an a-helix between residues Val(14) and Ser(20) in a mixed solvent. These studies are the first to elucidate the structure of human obestatin and provide clear evidence that the observed a-helical structures are critical for in vivo activity. Future structure/function studies may facilitate the design of novel therapeutic agents based on the obestatin peptide structure. (C) 2010 Elsevier Inc. All rights reserved.

Optical source model for the 23.2-23.6 nm radiation from the multielement germanium soft X-ray laser

Distributions of source intensity in two dimensions (designated the source model), averaged over a single laser pulse, based on experimental measurements of spatial coherence, are considered for radiation from the unresolved 23.2/23.6 nm spectral lines from the germanium collisional X-ray laser. The model derives from measurements of the visibility of Young slit interference fringes determined by a method based on the Wiener-Khinchin theorem. Output from amplifiers comprising three and four target elements have similar coherence properties in directions within the horizontal plane corresponding to strong plasma refraction effects and fitting the coherence data shows source dimensions (FWHM) are similar to 26 mu m (horizontal), significantly smaller than expected by direct imaging, and similar to 125 mu m (vertical: equivalent to the height of the driver excitation). (C) 1999 Elsevier Science B.V. All rights reserved.

Dependence of spatial coherence of 23.2-23.6-nm radiation on the geometry of a multielement germanium x-ray laser target

The spatial coherence of a nanosecond pulsed germanium collisionally excited x-ray laser is measured experimentally for three target configurations. The diagnostic is based on Young's slit interference fringes with a dispersing element to resolve the 23.2- and 23.6-nm spectral lines. Target configurations include a double-slab target, known as the injector, and geometries in which the injector image is image relayed to seed either an additional single-slab target or a second double-slab target. A special feature of this study is the observation of the change in the apparent source size with angle of refraction across the diverging laser beam. Source sizes derived with a Gaussian source model decrease from 44 mu m for the injector target by a variable factor of as much as 2, according to target configuration, for beams leaving the additional amplifiers after strong refraction in the plasma. (C) 1998 Optical Society of America [S0740-3224(98)00810-8].

Time dependence of the spatial coherence of the 23.6- and 23.2-nm radiation from the germanium soft-x-ray laser

The time dependence of the spatial coherence of the combined spectral lines at 23.2 and 23.6 nm from the Ge XXIII collisionally pumped soft-x-ray laser with a double-slab target is examined within a single nanosecond pulse by use of Young's interference fringes and a streak camera. High source intensity is linked with low spatial coherence and vice verse. Calculations of the source intensity, size, and position have also been made; these calculations refer to a single-slab source. Comparison between the observed and calculated intensities, and of the source sizes both calculated and derived from the Young's fringes by interpretation with a Gaussian model of source emission, show good agreement in general trends. (C) 1998 Optical Society of America [S0740-3224(98)01905-5].

Collisional exitation soft X-ray laser at 23.6 nm in a laser-produced cylindrical target

We have tested soft X-ray lasing in neon-like germanium with cylindrical targets where wave guiding and plasma confinement may affect lasing. An intense soft X-ray laser beam of 0.05 MW peak power and a narrow beam divergence (8 mrad) was produced at 23.6 nm with a 4 cm long straight cylindrical target of 0.72 mm inner diameter. Bending the cylindrical target to form a toroidal shape increased the lasing intensity by a factor of 3 accompanied with reduction of the beam divergence from 8 to 6 mrad.

SATURATED AND NEAR DIFFRACTION-LIMITED ASE OUTPUT AT 23.6 NM

Amplification of spontaneous emission at 23.6 nm has been studied in a Ge plasma heated by a 1 TW, 1.06 mum wavelength, laser pulse. The exponent of the axial gain reached 21 in a geometry with Fresnel number less-than-or-equal-to 1. Two plasma columns were produced by irradiation of slab targets up to a combined length of 3.6 cm. A narrow band XUV mirror allowed double pass amplification. Saturation of ASE output at 23.6 nm was observed as a change from exponential to linear growth of the output with plasma length. Further evidence of the effect was provided by a decline in the ratio of the output at 23.6 nm to that at 23.2 nm from approximately 1.6: 1 to approximately 0.5: 1, the latter being the theoretically predicted value for saturated operation. The onset of saturation at gL almost-equal-to 15 is consistent with model calculations. The beam divergence was about 8x diffraction limited with a brightness estimated at almost-equal-to 10(14) W/cm2/ster.

SATURATED AND NEAR-DIFFRACTION-LIMITED OPERATION OF AN XUV LASER AT 23.6 NM

Amplification of spontaneous emission (ASE) at 23.6 nm has been studied in a Ge plasma heated by a 1 TW infrared laser pulse. The exponent of the axial gain reached 21 in a geometry with Fresnel number less-than-or-equal-to 1. Two plasma columns of combined length up to 36 mm were used with an extreme ultraviolet mirror giving double-pass amplification. Saturation of the ASE output was observed. The beam divergence was about 8 x diffraction limited with a brightness estimated at 10(14) W cm-2 sr-1. The feedback from the mirror was significantly reduced probably by radiation damage from the plasma.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 EURODIAB centres during 1989-2008

Objectives: To investigate seasonal variation in month of diagnosis in children with type 1 diabetes registered in EURODIAB centres during 1989-2008.
Methods: 23 population-based registers recorded date of diagnosis in new cases of clinically diagnosed type 1 diabetes in children aged under 15 years. Completeness of ascertainment was assessed through capture-recapture methodology and was high in most centres. A general test for seasonal variation (11df) and Edward's test for sinusoidal (sine wave) variation (2df) were employed. Time series methods were also used to investigate if meteorological data were predictive of monthly counts after taking account of seasonality and long term trends.
Results: Significant seasonal variation was apparent in all but two small centres, with an excess of cases apparent in the winter quarter. Significant sinusoidal pattern was also evident in all but two small centres with peaks in December (14 centres), January (5 centres) or February (2 centres). Relative amplitude varied from ±11% to ±39% (median ±18%). There was no relationship across the centres between relative amplitude and incidence level. However there was evidence of significant deviation from the sinusoidal pattern in the majority of centres. Pooling results over centres, there was significant seasonal variation in each age-group at diagnosis, but with significantly less variation in those aged under 5 years. Boys showed marginally greater seasonal variation than girls. There were no differences in seasonal pattern between four sub-periods of the 20 year period. In most centres monthly counts of cases were not associated with deviations from normal monthly average temperature or sunshine hours; short term meteorological variations do not explain numbers of cases diagnosed.
Conclusions: Seasonality with a winter excess is apparent in all age-groups and both sexes, but girls and the under 5s show less marked variation. The seasonal pattern changed little in the 20 year period.