Antithrombotic actions of statins involve PECAM-1 signalling

Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment for coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Since several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1, we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signalling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1-/- platelets. Activation of PECAM-1 signalling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3-K) and diminished PI3-K signalling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provides evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs.

Molecular targets underlying SUMO-mediated neuroprotection in brain ischemia

SUMOylation (small ubiquitin-like modifier conjugation) is an important post-translational modification which is becoming increasingly implicated in the altered protein dynamics associated with brain ischemia. The function of SUMOylation in cells undergoing ischemic stress and the identity of small ubiquitin-like modifier (SUMO) targets remain in most cases unknown. However, the emerging consensus is that SUMOylation of certain proteins might be part of an endogenous neuroprotective response. This review brings together the current understanding of the underlying mechanisms and downstream effects of SUMOylation in brain ischemia, including processes such as autophagy, mitophagy and oxidative stress. We focus on recent advances and controversies regarding key central nervous system proteins, including those associated with the nucleus, cytoplasm and plasma membrane, such as glucose transporters (GLUT1, GLUT4), excitatory amino acid transporter 2 glutamate transporters, K+ channels (K2P1, Kv1.5, Kv2.1), GluK2 kainate receptors, mGluR8 glutamate receptors and CB1 cannabinoid receptors, which are reported to be SUMO-modified. A discussion of the roles of these molecular targets for SUMOylation could play following an ischemic event, particularly with respect to their potential neuroprotective impact in brain ischemia, is proposed.

The distribution of interplanetary dust between 0.96 and 1.04 au as inferred from impacts on the STEREO spacecraft observed by the heliospheric imagers

The distribution of dust in the ecliptic plane between 0.96 and 1.04 au has been inferred from impacts on the two Solar Terrestrial Relations Observatory (STEREO) spacecraft through observation of secondary particle trails and unexpected off-points in the heliospheric imager (HI) cameras. This study made use of analysis carried out by members of a distributed web-based citizen science project Solar Stormwatch. A comparison between observations of the brightest particle trails and a survey of fainter trails shows consistent distributions. While there is no obvious correlation between this distribution and the occurrence of individual meteor streams at Earth, there are some broad longitudinal features in these distributions that are also observed in sources of the sporadic meteor population. The different position of the HI instrument on the two STEREO spacecraft leads to each sampling different populations of dust particles. The asymmetry in the number of trails seen by each spacecraft and the fact that there are many more unexpected off-points in the HI-B than in HI-A indicates that the majority of impacts are coming from the apex direction. For impacts causing off-points in the HI-B camera, these dust particles are estimated to have masses in excess of 10−17 kg with radii exceeding 0.1 μm. For off-points observed in the HI-A images, which can only have been caused by particles travelling from the anti-apex direction, the distribution is consistent with that of secondary ‘storm’ trails observed by HI-B, providing evidence that these trails also result from impacts with primary particles from an anti-apex source. Investigating the mass distribution for the off-points of both HI-A and HI-B, it is apparent that the differential mass index of particles from the apex direction (causing off-points in HI-B) is consistently above 2. This indicates that the majority of the mass is within the smaller particles of this population. In contrast, the differential mass index of particles from the anti-apex direction (causing off-points in HI-A) is consistently below 2, indicating that the majority of the mass is to be found in larger particles of this distribution.

A finite element-spherical harmonics model for radiative transfer in inhomogeneous clouds. Part II. some applications

EVENT has been used to examine the effects of 3D cloud structure, distribution, and inhomogeneity on the scattering of visible solar radiation and the resulting 3D radiation field. Large eddy simulation and aircraft measurements are used to create realistic cloud fields which are continuous or broken with smooth or uneven tops. The values, patterns and variance in the resulting downwelling and upwelling radiation from incident visible solar radiation at different angles are then examined and compared to measurements. The results from EVENT confirm that 3D cloud structure is important in determining the visible radiation field, and that these results are strongly influenced by the solar zenith angle. The results match those from other models using visible solar radiation, and are supported by aircraft measurements of visible radiation, providing confidence in the new model.

The time-course of morphological constraints: Evidence from eye-movements during reading

Lexical compounds in English are constrained in that the non-head noun can be an irregular but not a regular plural (e.g. mice eater vs. *rats eater), a contrast that has been argued to derive from a morphological constraint on modifiers inside compounds. In addition, bare nouns are preferred over plural forms inside compounds (e.g. mouse eater vs. mice eater), a contrast that has been ascribed to the semantics of compounds. Measuring eyemovements during reading, this study examined how morphological and semantic information become available over time during the processing of a compound. We found that the morphological constraint affected both early and late eye-movement measures, whereas the semantic constraint for singular non-heads only affected late measures of processing. These results indicate that morphological information becomes available earlier than semantic information during the processing of compounds.

Explosive development of winter storm Xynthia over the subtropical North Atlantic Ocean

In winter of 2009–2010 south-western Europe was hit by several destructive windstorms. The most important was Xynthia (26–28 February 2010), which caused 64 reported casualties and was classified as the 2nd most expensive natural hazard event for 2010 in terms of economic losses. In this work we assess the synoptic evolution, dynamical characteristics and the main impacts of storm Xynthia, whose genesis, development and path were very uncommon. Wind speed gusts observed at more than 500 stations across Europe are evaluated as well as the wind gust field obtained with a regional climate model simulation for the entire North Atlantic and European area. Storm Xynthia was first identified on 25 February around 30° N, 50° W over the subtropical North Atlantic Ocean. Its genesis occurred on a region characterized by warm and moist air under the influence of a strong upper level wave embedded in the westerlies. Xynthia followed an unusual SW–NE path towards Iberia, France and central Europe. The role of moist air masses on the explosive development of Xynthia is analysed by considering the evaporative sources. A lagrangian model is used to identify the moisture sources, sinks and moisture transport associated with the cyclone during its development phase. The main supply of moisture is located over an elongated region of the subtropical North Atlantic Ocean with anomalously high SST, confirming that the explosive development of storm Xynthia had a significant contribution from the subtropics.

The extreme European summer 2012

The European summer of 2012 was marked by strongly contrasting rainfall anomalies, which led to flooding in northern Europe and droughts and wildfires in southern Europe. This season was not an isolated event, rather the latest in a string of summers characterized by a southward shifted Atlantic storm track as described by the negative phase of the SNAO. The degree of decadal variability in these features suggests a role for forcing from outside the dynamical atmosphere, and preliminary numerical experiments suggest that the global SST and low Arctic sea ice extent anomalies are likely to have played a role and that warm North Atlantic SSTs were a particular contributing factor. The direct effects of changes in radiative forcing from greenhouse gas and aerosol forcing are not included in these experiments, but both anthropogenic forcing and natural variability may have influenced the SST and sea ice changes.

Measuring large topographic change with InSAR: lava thicknesses, extrusion rate and subsidence rate at Santiaguito volcano, Guatemala

Lava flows can produce changes in topography on the order of 10s-100s of metres. A knowledge of the resulting volume change provides evidence about the dynamics of an eruption. We present a method to measure topographic changes from the differential InSAR phase delays caused by the height differences between the current topography and a Digital Elevation Model (DEM). This does not require a pre-event SAR image, so it does not rely on interferometric phase remaining coherent during eruption and emplacement. Synthetic tests predicts that we can estimate lava thickness of as little as �9 m, given a minimum of 5 interferograms with suitably large orbital baseine separations. In the case of continuous motion, such as lava flow subsidence, we invert interferometric phase simultaneously for topographic change and displacement. We demonstrate the method using data from Santiaguito volcano, Guatemala, and measure increases in lava thickness of up to 140 m between 2000 and 2009, largely associated with activity between 2000 and 2005. We find a mean extrusion rate of 0.43 +/- 0.06 m3/s, which lies within the error bounds of the longer term extrusion rate between 1922-2000. The thickest and youngest parts of the flow deposit were shown to be subsiding at an average rate of �-6 cm/yr. This is the first time that flow thickness and subsidence have been measured simultaneously. We expect this method to be suitable for measurment of landslides and other mass flow deposits as well as lava flows.

Sea-surface temperature records of Termination 1 in the Gulf of California: Challenges for seasonal and interannual analogues of tropical Pacific climate change

Centennial-scale records of sea-surface temperature and opal composition spanning the Last Glacial Maximum and Termination 1 (circa 25–6 ka) are presented here from Guaymas Basin in the Gulf of California. Through the application of two organic geochemistry proxies, the U37K′ index and the TEX86H index, we present evidence for rapid, stepped changes in temperatures during deglaciation. These occur in both temperature proxies at 13 ka (∼3°C increase in 270 years), 10.0 ka (∼2°C decrease over ∼250 years) and at 8.2 ka (3°C increase in <200 years). An additional rapid warming step is also observed in TEX86H at 11.5 ka. In comparing the two temperature proxies and opal content, we consider the potential for upwelling intensity to be recorded and link this millennial-scale variability to shifting Intertropical Convergence Zone position and variations in the strength of the Subtropical High. The onset of the deglacial warming from 17 to 18 ka is comparable to a “southern hemisphere” signal, although the opal record mimics the ice-rafting events of the north Atlantic (Heinrich events). Neither the modern seasonal cycle nor El Niño/Southern Oscillation patterns provide valid analogues for the trends we observe in comparison with other regional records. Fully coupled climate model simulations confirm this result, and in combination we question whether the seasonal or interannual climate variations of the modern climate are valid analogues for the glacial and deglacial tropical Pacific.

Rheology of discrete failure regimes of anisotropic sea ice

A rheological model of sea ice is presented that incorporates the orientational distribution of ice thickness in leads embedded in isotropic floe ice. Sea ice internal stress is determined by coulombic, ridging and tensile failure at orientations where corresponding failure criteria are satisfied at minimum stresses. Because sea ice traction increases in thinner leads and cohesion is finite, such failure line angles are determined by the orientational distribution of sea ice thickness relative to the imposed stresses. In contrast to the isotropic case, sea ice thickness anisotropy results in these failure lines becoming dependent on the stress magnitude. Although generally a given failure criteria type can be satisfied at many directions, only two at most are considered. The strain rate is determined by shearing along slip lines accompanied by dilatancy and closing or opening across orientations affected by ridging or tensile failure. The rheology is illustrated by a yield curve determined by combining coulombic and ridging failure for the case of two pairs of isotropically formed leads of different thicknesses rotated with regard to each other, which models two events of coulombic failure followed by dilatancy and refreezing. The yield curve consists of linear segments describing coulombic and ridging yield as failure switches from one lead to another as the stress grows. Because sliding along slip lines is accompanied by dilatancy, at typical Arctic sea ice deformation rates a one-day-long deformation event produces enough open water that these freshly formed slip lines are preferential places of ridging failure.

Aerosol absorption over the clear-sky oceans deduced from POLDER-1 and AERONET observations

We estimate aerosol absorption over the clear-sky oceans using aerosol geophysical products from POLDER-1 space measurements and absorption properties from ground-based AERONET measurements. Our best estimate is 2.5 Wm-2 averaged over the 8-month lifetime of POLDER-1. Low and high absorption estimates are 2.2 and 3.1 Wm-2 based on the variability in aerosol single scattering albedo observed by AERONET. Main sources of uncertainties are the discrimation of the aerosol type from satellite measurements, and potential clear-sky bias induced by the cloud-screening procedure.

The Joint UK Land Environment Simulator (JULES), model description – part 1: energy and water fluxes

This manuscript describes the energy and water components of a new community land surface model called the Joint UK Land Environment Simulator (JULES). This is developed from the Met Office Surface Exchange Scheme (MOSES). It can be used as a stand alone land surface model driven by observed forcing data, or coupled to an atmospheric global circulation model. The JULES model has been coupled to the Met Office Unified Model (UM) and as such provides a unique opportunity for the research community to contribute their research to improve both world-leading operational weather forecasting and climate change prediction systems. In addition JULES, and its forerunner MOSES, have been the basis for a number of very high-profile papers concerning the land-surface and climate over the last decade. JULES has a modular structure aligned to physical processes, providing the basis for a flexible modelling platform.

Intramolecular Diels-Alder furan-mediated synthesis of 8-aryl-3, 4-di-hydroisoquinolin-1(2H)-ones, convenient precursors of indeno[1,2,3-ij]isoquinolines

We describe herein preliminary studies on the Intramolecular Diels-Alder Furan-Mediated Synthesis of 8-Aryl-3, 4-di-hydroisoquinolin-1(2H)-ones that constitutes a new, formal synthesis of Indeno[1,2,3-ij]isoquinolines.

[Global climate] global aerosols [in state of the climate in 2008]

The global mean temperature in 2008 was slightly cooler than that in 2007; however, it still ranks within the 10 warmest years on record. Annual mean temperatures were generally well above average in South America, northern and southern Africa, Iceland, Europe, Russia, South Asia, and Australia. In contrast, an exceptional cold outbreak occurred during January across Eurasia and over southern European Russia and southern western Siberia. There has been a general increase in land-surface temperatures and in permafrost temperatures during the last several decades throughout the Arctic region, including increases of 1° to 2°C in the last 30 to 35 years in Russia. Record setting warm summer (JJA) air temperatures were observed throughout Greenland. The year 2008 was also characterized by heavy precipitation in a number of regions of northern South America, Africa, and South Asia. In contrast, a prolonged and intense drought occurred during most of 2008 in northern Argentina, Paraguay, Uruguay, and southern Brazil, causing severe impacts to agriculture and affecting many communities. The year began with a strong La Niña episode that ended in June. Eastward surface current anomalies in the tropical Pacific Ocean in early 2008 played a major role in adjusting the basin from strong La Niña conditions to ENSO-neutral conditions by July–August, followed by a return to La Niña conditions late in December. The La Niña conditions resulted in far-reaching anomalies such as a cooling in the central tropical Pacific, Arctic Ocean, and the regions extending from the Gulf of Alaska to the west coast of North America; changes in the sea surface salinity and heat content anomalies in the tropics; and total column water vapor, cloud cover, tropospheric temperature, and precipitation patterns typical of a La Niña. Anomalously salty ocean surface salinity values in climatologically drier locations and anomalously fresh values in rainier locations observed in recent years generally persisted in 2008, suggesting an increase in the hydrological cycle. The 2008 Atlantic hurricane season was the 14th busiest on record and the only season ever recorded with major hurricanes each month from July through November. Conversely, activity in the northwest Pacific was considerably below normal during 2008. While activity in the north Indian Ocean was only slightly above average, the season was punctuated by Cyclone Nargis, which killed over 145,000 people; in addition, it was the seventh-strongest cyclone ever in the basin and the most devastating to hit Asia since 1991. Greenhouse gas concentrations continued to rise, increasing by more than expected based on with CO2 the 1979 to 2007 trend. In the oceans, the global mean uptake for 2007 is estimated to be 1.67 Pg-C, about CO2 0.07 Pg-C lower than the long-term average, making it the third-largest anomaly determined with this method since 1983, with the largest uptake of carbon over the past decade coming from the eastern Indian Ocean. Global phytoplankton chlorophyll concentrations were slightly elevated in 2008 relative to 2007, but regional changes were substantial (ranging to about 50%) and followed long-term patterns of net decreases in chlorophyll with increasing sea surface temperature. Ozone-depleting gas concentrations continued to fall globally to about 4% below the peak levels of the 2000–02 period. Total column ozone concentrations remain well below pre-1980, levels and the 2008 ozone hole was unusually large (sixth worst on record) and persistent, with low ozone values extending into the late December period. In fact the polar vortex in 2008 persisted longer than for any previous year since 1979. Northern Hemisphere snow cover extent for the year was well below average due in large part to the record-low ice extent in March and despite the record-maximum coverage in January and the shortest snow cover duration on record (which started in 1966) in the North American Arctic. Limited preliminary data imply that in 2008 glaciers continued to lose mass, and full data for 2007 show it was the 17th consecutive year of loss. The northern region of Greenland and adjacent areas of Arctic Canada experienced a particularly intense melt season, even though there was an abnormally cold winter across Greenland's southern half. One of the most dramatic signals of the general warming trend was the continued significant reduction in the extent of the summer sea-ice cover and, importantly, the decrease in the amount of relatively older, thicker ice. The extent of the 2008 summer sea-ice cover was the second-lowest value of the satellite record (which started in 1979) and 36% below the 1979–2000 average. Significant losses in the mass of ice sheets and the area of ice shelves continued, with several fjords on the northern coast of Ellesmere Island being ice free for the first time in 3,000–5,500 years. In Antarctica, the positive phase of the SAM led to record-high total sea ice extent for much of early 2008 through enhanced equatorward Ekman transport. With colder continental temperatures at this time, the 2007–08 austral summer snowmelt season was dramatically weakened, making it the second shortest melt season since 1978 (when the record began). There was strong warming and increased precipitation along the Antarctic Peninsula and west Antarctica in 2008, and also pockets of warming along coastal east Antarctica, in concert with continued declines in sea-ice concentration in the Amundsen/Bellingshausen Seas. One significant event indicative of this warming was the disintegration and retreat of the Wilkins Ice Shelf in the southwest peninsula area of Antarctica.