7,8-dihydropyrido[2,3-d]pyrimidin-2-one; a bicyclic cytosine analogue capable of enhanced stabilisation of DNA duplexes

Incorporation of a bicyclic cytosine analogue, 3-beta-D-(2'-deoxyribofuranosyl)7,8- dihydropyrido[ 2,3-d] pyrimidine, into synthetic DNA duplexes results in a greatly enhanced thermal stability ( 3 - 4 degrees C per modification) compared to the corresponding unmodified duplex.

Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth

Consumption of anthocyanins has been related with beneficial health effects. However, bioavailability studies have shown low concentration of anthocyanins in plasma and urine. In this study, we have investigated the bacterial-dependent metabolism of malvidin-3-glucoside, gallic acid and a mixture of anthocyanins using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal human large intestine conditions. Most anthocyanins have disappeared after 5 h incubation while gallic acid remained constant through the first 5 h and was almost completely degraded following 24 h of fermentation. Incubation of malvidin-3-glucoside with fecal bacteria mainly resulted in the formation of syringic acid, while the mixture of anthocyanins resulted in formation of gallic, syringic and p-coumaric acids. All the anthocyanins tested enhanced significantly the growth of Bif idobacterium spp. and Lactobacillus−Enterococcus spp. These results suggest that anthocyanins and their metabolites may exert a positive modulation of the intestinal bacterial population.

Liquid-vapour homogenisation of fluid inclusions in stalagmites: Evaluation of a new thermometer for paleoclimate research

We present a new approach to determine palaeotemperatures (mean annual surface temperatures) based on measurements of the liquid–vapour homogenisation temperature of fluid inclusions in stalagmites. The aim of this study is to explore the potential and the limitations of this new palaeothermometer and to develop a reliable methodology for routine applications in palaeoclimate research. Therefore, we have investigated recent fluid inclusions from the top part of actively growing stalagmites that have formed at temperatures close to the present-day cave air temperature. A precondition for measuring homogenisation temperatures of originally monophase inclusions is the nucleation of a vapour bubble by means of single ultra-short laser pulses. Based on the observed homogenisation temperatures (Th(obs)) and measurements of the vapour bubble diameter at a known temperature, we calculated stalagmite formation temperatures (Tf) by applying a thermodynamic model that takes into account the effect of surface tension on liquid–vapour homogenisation. Results from recent stalagmite samples demonstrate that calculated stalagmite formation temperatures match the present-day cave air temperature within ± 0.2 °C. To avoid artificially induced changes of the fluid density we defined specific demands on the selection, handling and preparation of the stalagmite samples. Application of the method is restricted to stalagmites that formed at cave temperatures greater than ~ 9–11 °C.

Microbiological, chemical and rheological properties of low fat set yoghurt produced with exopolysaccharide (EPS) producing Bifidobacterium strains.

In this work, the microbiological and physicochemical differences of three types of low fat set yoghurts were studied, as well as the changes taking place during storage at 4 °C for 28 days. The first yoghurt was produced with yoghurt starters and exopolysaccharide (EPS) producing Bifidobacterium longum subsp. infantis CCUG 52486 (CCUGY), the second with yoghurt starters and Bifidobacterium infantis NCIMB 702205 (NCIMBY) and the third with just yoghurt starters (control yoghurt). No significant differences were observed in terms of cell concentrations; for all three yoghurts, similar final cell concentrations were obtained for the yoghurt starter cultures (~7.5 log cfu g−1) and the Bifidobacterium strains (~7.8 log cfu g−1). Both Bifidobacterium survived well during storage, as in both cases the cell viability decreased by less than 0.5 log cfu g−1after 28 days of storage. A decrease in pH followed by an increase in lactic acid was observed during storage for all three yoghurts, which was mostly attributed to the activity of the yoghurt starter cultures. The two yoghurts with the EPS producing Bifidobacterium strains exhibited lower syneresis than the control yoghurt. The lowest was shown by CCUGY, which also exhibited the highest storage modulus and firmness, and a well defined porous web-like structure in cryo-SEM. Examination of the micro-structure of the yoghurts using cryo-scanning electron microscopy (cryo-SEM) indicated that the above observations were due to the interaction between the EPS and the milk proteins. Overall, the results indicated that the EPS producing Bifidobacterium longum subsp. infantis CCUG 52486 is the most promising strain, and can be used with yoghurt starter cultures to manufacture low fat set yoghurt with probiotic activities and at the same time enhanced physicochemical and rheological properties.

Interaction of anthocyanins with human serum albumin: influence of pH and chemical structure on binding

The affinity of anthocyanins for human serum albumin (HSA) was determined by a fluorescence quenching method. The effects of pH and structure of anthocyanins on the binding constants were studied. The constants for binding of anthocyanins to HSA ranged from 1.08 x 10^5 M-1 to 13.16 x 10^5 M-1. A hydrophobic effect at acidic pH was shown by the relatively high positive entropy values under the conditions studied. Electrostatic interactions including hydrogen bonding contributed to the binding at pH 7.4. The effect of structure of anthocyanins on the affinity was pH dependent, particularly the effect of additional hydroxyl substituents. Hydroxyl substituents and glycosylation of anthocyanins decreased the affinity for binding to HSA at lower pH (especially pH 4), but increased the strength of binding at pH 7.4. In contrast, methylation of a hydroxyl group enhanced the binding at acidic pH, while this substitution reduced the strength of binding at pH 7.4. This paper has shown that changes in anthocyanin structure or reductions in pH, which may occur in the region of inflammatory sites, have an effect of the binding of anthocyanins to HSA.

The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo

BACKGROUND: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. METHODS: Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. RESULTS: Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. CONCLUSIONS: These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.

Extended optimal estimation techniques for sea surface temperature from the Spinning Enhanced Visible and Infra-Red Imager (SEVIRI)

Sea surface temperature (SST) can be estimated from day and night observations of the Spinning Enhanced Visible and Infra-Red Imager (SEVIRI) by optimal estimation (OE). We show that exploiting the 8.7 μm channel, in addition to the “traditional” wavelengths of 10.8 and 12.0 μm, improves OE SST retrieval statistics in validation. However, the main benefit is an improvement in the sensitivity of the SST estimate to variability in true SST. In a fair, single-pixel comparison, the 3-channel OE gives better results than the SST estimation technique presently operational within the Ocean and Sea Ice Satellite Application Facility. This operational technique is to use SST retrieval coefficients, followed by a bias-correction step informed by radiative transfer simulation. However, the operational technique has an additional “atmospheric correction smoothing”, which improves its noise performance, and hitherto had no analogue within the OE framework. Here, we propose an analogue to atmospheric correction smoothing, based on the expectation that atmospheric total column water vapour has a longer spatial correlation length scale than SST features. The approach extends the observations input to the OE to include the averaged brightness temperatures (BTs) of nearby clear-sky pixels, in addition to the BTs of the pixel for which SST is being retrieved. The retrieved quantities are then the single-pixel SST and the clear-sky total column water vapour averaged over the vicinity of the pixel. This reduces the noise in the retrieved SST significantly. The robust standard deviation of the new OE SST compared to matched drifting buoys becomes 0.39 K for all data. The smoothed OE gives SST sensitivity of 98% on average. This means that diurnal temperature variability and ocean frontal gradients are more faithfully estimated, and that the influence of the prior SST used is minimal (2%). This benefit is not available using traditional atmospheric correction smoothing.

Estimation of sea surface temperature from the Spinning Enhanced Visible and Infra Red Imager, improved using numerical weather prediction

Most of the operational Sea Surface Temperature (SST) products derived from satellite infrared radiometry use multi-spectral algorithms. They show, in general, reasonable performances with root mean square (RMS) residuals around 0.5 K when validated against buoy measurements, but have limitations, particularly a component of the retrieval error that relates to such algorithms' limited ability to cope with the full variability of atmospheric absorption and emission. We propose to use forecast atmospheric profiles and a radiative transfer model to simulate the algorithmic errors of multi-spectral algorithms. In the practical case of SST derived from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard Meteosat Second Generation (MSG), we demonstrate that simulated algorithmic errors do explain a significant component of the actual errors observed for the non linear (NL) split window algorithm in operational use at the Centre de Météorologie Spatiale (CMS). The simulated errors, used as correction terms, reduce significantly the regional biases of the NL algorithm as well as the standard deviation of the differences with drifting buoy measurements. The availability of atmospheric profiles associated with observed satellite-buoy differences allows us to analyze the origins of the main algorithmic errors observed in the SEVIRI field of view: a negative bias in the inter-tropical zone, and a mid-latitude positive bias. We demonstrate how these errors are explained by the sensitivity of observed brightness temperatures to the vertical distribution of water vapour, propagated through the SST retrieval algorithm.

The potential impact of changes in lower stratospheric water vapour on stratospheric temperatures over the past 30 years

This study investigates the potential contribution of observed changes in lower stratospheric water vapour to stratospheric temperature variations over the past three decades using a comprehensive global climate model (GCM). Three case studies are considered. In the first, the net increase in stratospheric water vapour (SWV) from 1980–2010 (derived from the Boulder frost-point hygrometer record using the gross assumption that this is globally representative) is estimated to have cooled the lower stratosphere by up to ∼0.2 K decade−1 in the global and annual mean; this is ∼40% of the observed cooling trend over this period. In the Arctic winter stratosphere there is a dynamical response to the increase in SWV, with enhanced polar cooling of 0.6 K decade−1 at 50 hPa and warming of 0.5 K decade−1 at 1 hPa. In the second case study, the observed decrease in tropical lower stratospheric water vapour after the year 2000 (imposed in the GCM as a simplified representation of the observed changes derived from satellite data) is estimated to have caused a relative increase in tropical lower stratospheric temperatures by ∼0.3 K at 50 hPa. In the third case study, the wintertime dehydration in the Antarctic stratospheric polar vortex (again using a simplified representation of the changes seen in a satellite dataset) is estimated to cause a relative warming of the Southern Hemisphere polar stratosphere by up to 1 K at 100 hPa from July–October. This is accompanied by a weakening of the westerly winds on the poleward flank of the stratospheric jet by up to 1.5 m s−1 in the GCM. The results show that, if the measurements are representative of global variations, SWV should be considered as important a driver of transient and long-term variations in lower stratospheric temperature over the past 30 years as increases in long-lived greenhouse gases and stratospheric ozone depletion.

Global radiative and climate effect of the water vapour continuum at visible and near-infrared wavelengths

Recent laboratory measurements show that absorption by the water vapour continuum in near-infrared windows may be about an order of magnitude higher than assumed in many radiation codes. The radiative impact of the continuum at visible and near-infrared wavelengths is examined for the present day and for a possible future warmer climate (with a global-mean total column water increase of 33%). The calculations use a continuum model frequently used in climate models (‘CKD’) and a continuum model where absorption is enhanced at wavelengths greater than 1 µm based on recent measurements (‘CAVIAR’). The continuum predominantly changes the partitioning between solar radiation absorbed by the surface and the atmosphere; changes in top-of-atmosphere net irradiances are smaller. The global-mean clear-sky atmospheric absorption is enhanced by 1.5 W m−2 (about 2%) and 2.8 W m−2 (about 3.5%) for CKD and CAVIAR respectively, relative to a hypothetical no-continuum case, with all-sky enhancements about 80% of these values. The continuum is, in relative terms, more important for radiation budget changes between the present day and a possible future climate. Relative to the no-continuum case, the increase in global-mean clear-sky absorption is 8% higher using CKD and almost 20% higher using CAVIAR; all-sky enhancements are about half these values. The effect of the continuum is estimated for the solar component of the water vapour feedback, the reduction in downward surface irradiance and precipitation change in a warmer world. For CKD and CAVIAR respectively, and relative to the no-continuum case, the solar component of the water vapour feedback is enhanced by about 4 and 9%, the change in clear-sky downward surface irradiance is 7 and 18% more negative, and the global-mean precipitation response decreases by 1 and 4%. There is a continued need for improved continuum measurements, especially at atmospheric temperatures and at wavelengths below 2 µm.

Enhanced MALDI MS sensitivity by weak base additives and glycerol sample coating

The concept of rationally designing MALDI matrices has been extended to the next “whole sample” level. These studies have revealed some unexpected and exploitable insights in improving MALDI sensitivity. It is shown that (i) additives which only provide additional laser energy absorption are best to be avoided; (ii) the addition of proton donors in the form of protonated weak bases can be highly beneficial; (iii) the addition of glycerol for coating crystalline samples is highly recommended. Overall, analytical sensitivity has been significantly increased compared to the current “gold” standards in MALDI MS, and new insights into the mechanisms and processes of MALDI have been gained.

Plasma structure within poleward-moving cusp/cleft auroral transients: EISCAT Svalbard radar observations and an explanation in terms of large local time extent of events

We report high-resolution observations of the southward-IMF cusp/cleft ionosphere made on December 16th 1998 by the EISCAT (European incoherent scatter) Svalbard radar (ESR), and compare them with observations of dayside auroral luminosity, as seen at a wavelength of 630 nm by a meridian scanning photometer at Ny Alesund, and of plasma flows, as seen by the CUTLASS (co-operative UK twin location auroral sounding system) Finland HF radar. The optical data reveal a series of poleward-moving transient red-line (630 nm) enhancements, events that have been associated with bursts in the rate of magnetopause reconnection generating new open flux. The combined observations at this time have strong similarities to predictions of the effects of soft electron precipitation modulated by pulsed reconnection, as made by Davis and Lockwood (1996); however, the effects of rapid zonal flow in the ionosphere, caused by the magnetic curvature force on the newly opened field lines, are found to be a significant additional factor. In particular, it is shown how enhanced plasma loss rates induced by the rapid convection can explain two outstanding anomalies of the 630 nm transients, namely how minima in luminosity form between the poleward-moving events and how events can re-brighten as they move poleward. The observations show how cusp/cleft aurora and transient poleward-moving auroral forms appear in the ESR data and the conditions which cause enhanced 630 nm emission in the transients: they are an important first step in enabling the ESR to identify these features away from the winter solstice when supporting auroral observations are not available.

Temporal and spatial variability of auroral forms in the 10–14 MLT sector: Relationship to plasma convection and solar wind-magnetosphere coupling

Ground-based observations of dayside auroral forms and magnetic perturbations in the arctic sectors of Svalbard and Greenland, in combination with the high-resolution measurements of ionospheric ion drift and temperature by the EISCAT radar, are used to study temporal/spatial structures of cusp-type auroral forms in relation to convection. Large-scale patterns of equivalent convection in the dayside polar ionosphere are derived from the magnetic observations in Greenland and Svalbard. This information is used to estimate the ionospheric convection pattern in the vicinity of the cusp/cleft aurora. The reported observations, covering the period 0700-1130 UT, on January 11, 1993, are separated into four intervals according to the observed characteristics of the aurora and ionospheric convection. The morphology and intensity of the aurora are very different in quiet and disturbed intervals. A latitudinally narrow zone of intense and dynamical 630.0 nm emission equatorward of 75 degrees MLAT, was observed during periods of enhanced antisunward convection in the cusp region. This (type 1 cusp aurora) is considered to be the signature of plasma entry via magnetopause reconnection at low magnetopause latitudes, i.e. the low-latitude boundary layer (LLB I,). Another zone of weak 630.0 nm emission (type 2 cusp aurora) was observed to extend up to high latitudes (similar to 79 degrees MLAT) during relatively quiet magnetic conditions, when indications of reverse (sunward) convection was observed in the dayside polar cap. This is postulated to be a signature of merging between a northward directed IMF (B-z > 0) and the geomagnetic field poleward of the cusp. The coexistence of type 1 and 2 auroras was observed under intermediate circumstances. The optical observations from Svalbard and Greenland were also used to determine the temporal and spatial evolution of type 1 auroral forms, i.e. poleward-moving auroral events occurring in the vicinity of a rotational convection reversal in the early post-noon sector. Each event appeared as a local brightening at the equatorward boundary of the pre-existing type 1 cusp aurora, followed by poleward and eastward expansions of luminosity. The auroral events were associated with poleward-moving surges of enhanced ionospheric convection and F-layer ion temperature as observed by the EISCAT radar in Tromso. The EISCAT ion flow data in combination with the auroral observations show strong evidence for plasma flow across the open/closed field line boundary.