Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (M-w < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.

Evaluating the structure and magnitude of the ash plume during the initial phase of the 2010 Eyjafjallajökull eruption using lidar observations and NAME simulations

The Eyjafjallajökull volcano in Iceland erupted explosively on 14 April 2010, emitting a plume of ash into the atmosphere. The ash was transported from Iceland toward Europe where mostly cloud-free skies allowed ground-based lidars at Chilbolton in England and Leipzig in Germany to estimate the mass concentration in the ash cloud as it passed overhead. The UK Met Office's Numerical Atmospheric-dispersion Modeling Environment (NAME) has been used to simulate the evolution of the ash cloud from the Eyjafjallajökull volcano during the initial phase of the ash emissions, 14–16 April 2010. NAME captures the timing and sloped structure of the ash layer observed over Leipzig, close to the central axis of the ash cloud. Relatively small errors in the ash cloud position, probably caused by the cumulative effect of errors in the driving meteorology en route, result in a timing error at distances far from the central axis of the ash cloud. Taking the timing error into account, NAME is able to capture the sloped ash layer over the UK. Comparison of the lidar observations and NAME simulations has allowed an estimation of the plume height time series to be made. It is necessary to include in the model input the large variations in plume height in order to accurately predict the ash cloud structure at long range. Quantitative comparison with the mass concentrations at Leipzig and Chilbolton suggest that around 3% of the total emitted mass is transported as far as these sites by small (<100 μm diameter) ash particles.

A stress-controlled mechanism for the intensity of very large magnitude explosive eruptions

Large magnitude explosive eruptions are the result of the rapid and large-scale transport of silicic magma stored in the Earth's crust, but the mechanics of erupting teratonnes of silicic magma remain poorly understood. Here, we demonstrate that the combined effect of local crustal extension and magma chamber overpressure can sustain linear dyke-fed explosive eruptions with mass fluxes in excess of 10^10 kg/s from shallow-seated (4–6 km depth) chambers during moderate extensional stresses. Early eruption column collapse is facilitated with eruption duration of the order of few days with an intensity of at least one order of magnitude greater than the largest eruptions in the 20th century. The conditions explored in this study are one way in which high mass eruption rates can be achieved to feed large explosive eruptions. Our results corroborate geological and volcanological evidences from volcano-tectonic complexes such as the Sierra Madre Occidental (Mexico) and the Taupo Volcanic Zone (New Zealand).

A mechanism for the effect of tropospheric jet structure on the annular mode-like response to stratospheric forcing

For many climate forcings the dominant response of the extratropical circulation is a latitudinal shift of the tropospheric mid-latitude jets. The magnitude of this response appears to depend on climatological jet latitude in general circulation models (GCMs): lower latitude jets exhibit a larger shift. The reason for this latitude dependence is investigated for a particular forcing, heating of the equatorial stratosphere, which shifts the jet poleward. Spin-up ensembles with a simplified GCM are used to examine the evolution of the response for five different jet structures. These differ in the latitude of the eddy-driven jet, but have similar sub-tropical zonal winds. It is found that lower latitude jets exhibit a larger response due to stronger tropospheric eddy-mean flow feedbacks. A dominant feedback responsible for enhancing the poleward shift is an enhanced equatorward refraction of the eddies, resulting in an increased momentum flux, poleward of the low latitude critical line. The sensitivity of feedback strength to jet structure is associated with differences in the coherence of this behaviour across the spectrum of eddy phase speeds. In the configurations used, the higher latitude jets have a wider range of critical latitude locations. This reduces the coherence of the momentum flux anomalies associated with different phase speeds, with low phase speeds opposing the effect of high phase speeds. This suggests that, for a given sub-tropical zonal wind strength, the latitude of the eddy driven jet affects the feedback through its influence on the width of the region of westerly winds and the range of critical latitudes on the equatorward flank of the jet.

Ocean heat uptake and its consequences for the magnitude of sea level rise and climate change

Under increasing greenhouse gas concentrations, ocean heat uptake moderates the rate of climate change, and thermal expansion makes a substantial contribution to sea level rise. In this paper we quantify the differences in projections among atmosphere-ocean general circulation models of the Coupled Model Intercomparison Project in terms of transient climate response, ocean heat uptake efficiency and expansion efficiency of heat. The CMIP3 and CMIP5 ensembles have statistically indistinguishable distributions in these parameters. The ocean heat uptake efficiency varies by a factor of two across the models, explaining about 50% of the spread in ocean heat uptake in CMIP5 models with CO2 increasing at 1%/year. It correlates with the ocean global-mean vertical profiles both of temperature and of temperature change, and comparison with observations suggests the models may overestimate ocean heat uptake and underestimate surface warming, because their stratification is too weak. The models agree on the location of maxima of shallow ocean heat uptake (above 700 m) in the Southern Ocean and the North Atlantic, and on deep ocean heat uptake (below 2000 m) in areas of the Southern Ocean, in some places amounting to 40% of the top-to-bottom integral in the CMIP3 SRES A1B scenario. The Southern Ocean dominates global ocean heat uptake; consequently the eddy-induced thickness diffusivity parameter, which is particularly influential in the Southern Ocean, correlates with the ocean heat uptake efficiency. The thermal expansion produced by ocean heat uptake is 0.12 m YJ−1, with an uncertainty of about 10% (1 YJ = 1024 J).

Examining the large-scale spatial coherence of European drought using regional indicators of precipitation and streamflow deficit

Droughts tend to evolve slowly and affect large areas simultaneously, which suggests that improved understanding of spatial coherence of drought would enable better mitigation of drought impacts through enhanced monitoring and forecasting strategies. This study employs an up-to-date dataset of over 500 river flow time series from 11 European countries, along with a gridded precipitation dataset, to examine the spatial coherence of drought in Europe using regional indicators of precipitation and streamflow deficit. The drought indicators were generated for 24 homogeneous regions and, for selected regions, historical drought characteristics were corroborated with previous work. The spatial coherence of drought characteristics was then examined at a European scale. Historical droughts generally have distinctive signatures in their spatio-temporal development, so there was limited scope for using the evolution of historical events to inform forecasting. Rather, relationships were explored in time series of drought indicators between regions. Correlations were generally low, but multivariate analyses revealed broad continental-scale patterns, which appear to be related to large-scale atmospheric circulation indices (in particular, the North Atlantic Oscillation and the East Atlantic West Russia pattern). A novel methodology for forecasting was developed (and demonstrated with reference to the United Kingdom), which predicts drought from drought i.e. uses spatial coherence of drought to facilitate early warning of drought in a target region, from drought which is developing elsewhere in Europe.Whilst the skill of the methodology is relatively modest at present, this approach presents a potential new avenue for forecasting, which offers significant advantages in that it allows prediction for all seasons, and also shows some potential for forecasting the termination of drought conditions.

Does neural input or processing play a greater role in the magnitude of neuroimaging signals?

An important constraint on how hemodynamic neuroimaging signals such as fMRI can be interpreted in terms of the underlying evoked activity is an understanding of neurovascular coupling mechanisms that actually generate hemodynamic responses. The predominant view at present is that the hemodynamic response is most correlated with synaptic input and subsequent neural processing rather than spiking output. It is still not clear whether input or processing is more important in the generation of hemodynamics responses. In order to investigate this we measured the hemodynamic and neural responses to electrical whisker pad stimuli in rat whisker barrel somatosensory cortex both before and after the local cortical injections of the GABAA agonist muscimol. Muscimol would not be expected to affect the thalamocortical input into the cortex but would inhibit subsequent intra-cortical processing. Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously. Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by ∼79% compared to that elicited pre-infusion. The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

Real estate markets and the macroeconomy: a dynamic coherence framework

This paper analyzes the dynamic interactions between real estate markets, in the US and the UK and their macroeconomic environments. We apply a new approach based on a dynamic coherence function (DCF) to study these interactions bringing together different real estate markets (the securitized market, the commercial market and the residential market). The results suggest that there is a common trend that drives the different real estate markets in the UK and the US, particularly in the long run, since they have a similar shape of the DCF. We also find that, in the US, wealth and housing expenditure channels are very conductive during real estate crises. However, in the UK, only the wealth effect is significant as a transmission channel during real estate market downturns. In addition, real estate markets in the UK and the US react differently to institutional shocks. This brings some insights on the conduct of monetary policy in order to avoid disturbances in real estate markets.

Tempo, magnitude e o mito do cinema moderno

Neste texto, irei abordar três filmes ambientados em Portugal, cujas locações oferecem uma visão privilegiada da função do tempo e da magnitude no cinema, os quais, por sua vez, nos permitem reavaliar as categorias de clássico, moderno e pós-moderno aplicadas a esse meio. Trata-se de O estado das coisas (Der Stand der Dinge, Wim Wenders, 1982), Terra estrangeira (Walter Salles and Daniela Thomas, 1995) e Mistérios de Lisboa (Raúl Ruiz, 2010). Neles, a cidade se compõe de círculos viciosos, espelhos, réplicas e mise-en-abyme que interrompem o movimento vertiginoso característico da cidade modernista do cinema dos anos 20. Curiosamente, é também o lugar em que a assim chamada estética pós-moderna finalmente encontra abrigo em contos auto-irônicos que expõem as insuficiências dos mecanismos narrativos no cinema. Para compensá-las, recorre-se a procedimentos de intermídia, tais como fotografias de polaroid em O estado das coisas ou um teatro de papelão em Mistérios de Lisboa, que transformam uma realidade incomensurável em miniaturas fáceis de enquadrar e manipular. O real assim diminuído, no entanto, se revela um simulacro decepcionante, um ersatz da memória que evidencia o caráter ilusório da teleologia cosmopolita. Em minha abordagem, começarei por examinar a gênese interligada e transnacional desses filmes que resultou em três visões correlatas mas muito diversas do fim da história e da narrativa, típico da estética pós-moderna. A seguir, irei considerar o miniaturismo intermedial como uma tentativa de congelar o tempo no interior do movimento, uma equação que inevitavelmente nos remete ao binário deleuziano tempo-movimento, que também irei revisitar com o fim de distingui-lo da oposição entre cinema clássico e moderno. Por fim, irei propor a stasis reflexiva e a inversão de escala como demonominadores comuns entre todos os projetos ditos modernos, que por esta razão, segundo creio, são mais confiáveis que a modernidade enquanto indicadores de valores artísticos e políticos.

Elephants in pyjamas: testing the weak central coherence account of autism spectrum disorders using a syntactic disambiguation task

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status.

Corticomuscular coherence modulation with the pattern of finger force coordination

We assess the corticomuscular coherence (CMC) of the contralateral primary motor cortex and the hand muscles during a finger force-tracking task and explore whether the pattern of finger coordination has an impact on the CMC level. Six healthy subjects (three men and three women) were recruited to conduct the force-tracking tasks comprising two finger patterns, i.e., natural combination of index and middle fingers and unnatural combination of index and middle fingers (i.e., simultaneously producing equal force strength in index and middle finger). During the conducting of the tasks with right index and middle finger, MEG and sEMG signals were recorded from left primary motor cortex (M1) and right flexor digitorum superficialis (FDS), respectively; the contralateral CMC was calculated to assess the neuromuscular interaction. Finger force-tracking tasks of Common-IM only induce beta-band CMC, whereas Uncommon-IM tasks produce CMC in both beta and low-gamma band. Compared to the force-tracking tasks of Common-IM, the Uncommon-IM task is associated with the most intensive contralateral CMC. Our study demonstrated that the pattern of finger coordination had significant impact on the CMC between the contralateral M1 and hand muscles, and more corticomuscular interaction was necessary for unnaturally coordinated finger activities to regulate the fixed neural drive of hand muscles.

Diagnostic tool to analyse colour-magnitude diagrams of poorly populated stellar concentrations

The dynamical processes that lead to open cluster disruption cause its mass to decrease. To investigate such processes from the observational point of view, it is important to identify open cluster remnants (OCRs), which are intrinsically poorly populated. Due to their nature, distinguishing them from field star fluctuations is still an unresolved issue. In this work, we developed a statistical diagnostic tool to distinguish poorly populated star concentrations from background field fluctuations. We use 2MASS photometry to explore one of the conditions required for a stellar group to be a physical group: to produce distinct sequences in a colour-magnitude diagram (CMD). We use automated tools to (i) derive the limiting radius; (ii) decontaminate the field and assign membership probabilities; (iii) fit isochrones; and (iv) compare object and field CMDs, considering the isochrone solution, in order to verify the similarity. If the object cannot be statistically considered as a field fluctuation, we derive its probable age, distance modulus, reddening and uncertainties in a self-consistent way. As a test, we apply the tool to open clusters and comparison fields. Finally, we study the OCR candidates DoDz 6, NGC 272, ESO 435 SC48 and ESO 325 SC15. The tool is optimized to treat these low-statistic objects and to separate the best OCR candidates for studies on kinematics and chemical composition. The study of the possible OCRs will certainly provide a deep understanding of OCR properties and constraints for theoretical models, including insights into the evolution of open clusters and dissolution rates.