Bile salt composition is secondary to bile salt concentration in determining hydrocortisone and progesterone solubility in intestinal mimetic fluids.

Simulated intestinal fluids (SIFs) used to assay the solubility of orally administered drugs are typically based on a single bile salt; sodium taurocholate (STC). The aim of this study was to develop mimetic intestinal fluids with a closer similarity to physiological fluids than those reported to date by developing a mixed bile salt (MBS) system (STC, sodium glycodeoxycholate, sodium deoxycholate; 60:39:1) with different concentrations of lecithin, the preponderant intestinal phospholipid. Hydrocortisone and progesterone were used as model drugs to evaluate systematically the influence of SIF composition on solubility. Increasing total bile salt concentration from 0 to 30 mM increased hydrocortisone and progesterone solubility by 2- and ∼25-fold, respectively. Accordingly, higher solubilities were measured in the fed-state compared to the fasted-state SIFs. Progesterone showed the greatest increases in solubility in STC and MBS systems (2-7-fold) compared to hydrocortisone (no significant change; P>0.05) as lecithin concentration was increased. Overall, MBS systems gave similar solubility profiles to STC. In conclusion, the addenda of MBS and lecithin were found to be secondary to the influence of BS concentration. These data provide a foundation for the design of more bio-similar media for pivotal decision-guiding assays in drug development and quality control settings.

Self-assembly of a Model Peptide incorporating a Hexa-Histidine sequence attached to an Oligo-Alanine sequence, and binding to Gold NTA/Nickel nanoparticles

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

Divergent evolution of the activity and regulation of the glutamate decarboxylase systems in Listeria monocytogenes EGD-e and 10403S : roles in virulence and acid tolerance

The glutamate decarboxylase (GAD) system has been shown to be important for the survival of Listeria monocytogenes in low pH environments. The bacterium can use this faculty to maintain pH homeostasis under acidic conditions. The accepted model for the GAD system proposes that the antiport of glutamate into the bacterial cell in exchange for γ-aminobutyric acid (GABA) is coupled to an intracellular decarboxylation reaction of glutamate into GABA that consumes protons and therefore facilitates pH homeostasis. Most strains of L. monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a glutamate decarboxylase dedicated to the intracellular GAD system (GADi), which produces GABA from cytoplasmic glutamate in the absence of antiport activity. We also compare the functionality of the GAD system between two commonly studied reference strains, EGD-e and 10403S with differences in terms of acid resistance. Through functional genomics we show that EGD-e is unable to export GABA and relies exclusively in the GADi system, which is driven primarily by GadD3 in this strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular and extracellular GAD system (GADi/GADe). Through experiments with a murinised variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant role in the overall virulence of this strain. Double mutants lacking either gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were significantly affected in their ability to cause infection following oral inoculation. Since EGDm exploits GADi but not GADe the results indicate that the GADi system makes a contribution to virulence within the mouse. Furthermore, we also provide evidence that there might be a separate line of evolution in the GAD system between two commonly used reference strains.

On the relation between explosive cyclones affecting Europe and the North Atlantic oscillation

Intense winter cyclones often lead to hazardous weather over Europe. Previous studies have pointed to a link between the North Atlantic Oscillation (NAO) and strong European windstorms. However, the robustness of this relation for cyclones of varying intensities remains largely unexplored. In this paper, the bi-directional relation between the NAO and cyclones impacting Europe is analyzed for the period 1950–2010 focusing on the sensitivity to storm intensity. Evidence is given that explosive (EC) and non-explosive cyclones (NoEC) predominantly develop under different large-scale circulation conditions over the North Atlantic. Whereas NoEC evolve more frequently under negative and neutral NAO phases, the number of EC is larger under a positive NAO phase, typically characterized by an intensified jet toward Western Europe. Important differences are also found on the dynamics of NAO evolution after peak intensity for both cyclone populations.

Effective separation of Am(III) and Eu(III) from HNO3 Q1 Q2 solutions using CyMe4-BTPhen-functionalized silica-coated magnetic nanoparticles

It has been shown that CyMe4-BTPhen-functionalized silica-coated maghemite (c-Fe2O3) magnetic nanoparticles (MNPs) are capable of quantitative separation of Am(III) from Eu(III) from HNO3 solutions. These MNPs also show a small but significant selectivity for Am(III) over Cm(III) with a separation factor of around 2 in 4 M HNO3. The water molecule in the cavity of the BTPhen may also play an important part in the selectivity.

The statistical downscaling model-decision centric (SDSM-DC): conceptual basis and applications

Regional climate downscaling has arrived at an important juncture. Some in the research community favour continued refinement and evaluation of downscaling techniques within a broader framework of uncertainty characterisation and reduction. Others are calling for smarter use of downscaling tools, accepting that conventional, scenario-led strategies for adaptation planning have limited utility in practice. This paper sets out the rationale and new functionality of the Decision Centric (DC) version of the Statistical DownScaling Model (SDSM-DC). This tool enables synthesis of plausible daily weather series, exotic variables (such as tidal surge), and climate change scenarios guided, not determined, by climate model output. Two worked examples are presented. The first shows how SDSM-DC can be used to reconstruct and in-fill missing records based on calibrated predictor-predictand relationships. Daily temperature and precipitation series from sites in Africa, Asia and North America are deliberately degraded to show that SDSM-DC can reconstitute lost data. The second demonstrates the application of the new scenario generator for stress testing a specific adaptation decision. SDSM-DC is used to generate daily precipitation scenarios to simulate winter flooding in the Boyne catchment, Ireland. This sensitivity analysis reveals the conditions under which existing precautionary allowances for climate change might be insufficient. We conclude by discussing the wider implications of the proposed approach and research opportunities presented by the new tool.

A study on the sensitivities of simulated aerosol optical properties to composition and size distribution using airborne measurements

We present a flexible framework to calculate the optical properties of atmospheric aerosols at a given relative humidity based on their composition and size distribution. The similarity of this framework to climate model parameterisations allows rapid and extensive sensitivity tests of the impact of uncertainties in data or of new measurements on climate relevant aerosol properties. The data collected by the FAAM BAe-146 aircraft during the EUCAARI-LONGREX and VOCALS-REx campaigns have been used in a closure study to analyse the agreement between calculated and measured aerosol optical properties for two very different aerosol types. The agreement achieved for the EUCAARI-LONGREX flights is within the measurement uncertainties for both scattering and absorption. However, there is poor agreement between the calculated and the measured scattering for the VOCALS-REx flights. The high concentration of sulphate, which is a scattering aerosol with no absorption in the visible spectrum, made the absorption measurements during VOCALS-REx unreliable, and thus no closure study was possible for the absorption. The calculated hygroscopic scattering growth factor overestimates the measured values during EUCAARI-LONGREX and VOCALS-REx by ∼30% and ∼20%, respectively. We have also tested the sensitivity of the calculated aerosol optical properties to the uncertainties in the refractive indices, the hygroscopic growth factors and the aerosol size distribution. The largest source of uncertainty in the calculated scattering is the aerosol size distribution (∼35%), followed by the assumed hygroscopic growth factor for organic aerosol (∼15%), while the predominant source of uncertainty in the calculated absorption is the refractive index of organic aerosol (28–60%), although we would expect the refractive index of black carbon to be important for aerosol with a higher black carbon fraction.

Exposure to foods’ non-taste sensory properties: a nursery intervention to increase children’s willingness to try fruit and vegetables

Activities that engage young children with the sensory properties of foods are popular with nursery schools, despite the lack of evidence for their efficacy in increasing children's consumption of healthy foods. This study provides the first empirical exploration of the effectiveness of a non-taste sensory activity program in a nursery school setting. Ninety-two children aged between 12 and 36 months were allocated to either an intervention group, who took part in looking, listening, feeling and smelling activities with unusual fruits and vegetables every day for four weeks, or to a non-intervention control group. In a subsequent mealtime taste test, children touched and tasted more of the vegetables to which they had been familiarized in their playtime activities than of a matched set of non-exposed foods. The results demonstrate that hands-on activities with unfamiliar fruits and vegetables can enhance children’s willingness to taste these foods, and confirm the potential for such activities to support healthy eating initiatives.

Physiological and behavioral patterns of corruption

We study the behavior and emotional arousal of the participants in an experimental auction, leading to an asymmetric social dilemma involving an auctioneer and two bidders. An antisocial transfer (bribe) which is beneficial for the auctioneer (official) is paid, if promised, by the winner of the auction. Some pro-social behavior on both the auctioneers' and the bidders' sides is observed even in the absence of any punishment mechanism (Baseline, Treatment 0). However, pro-social behavior is adopted by the vast majority of subjects when the loser of the auction can inspect the transaction between the winner and the auctioneer (Inspection, Treatment 1). The inspection and punishment mechanism is such that, if a bribe is (not) revealed, both corrupt agents (the denouncing bidder) lose(s) this period's payoffs. This renders the inspection option unprofitable for the loser and is rarely used, especially towards the end of the session, when pro-social behavior becomes pervasive. Subjects' emotional arousal was obtained through skin conductance responses. Generally speaking, our findings suggest that stronger emotions are associated with decisions deviating from pure monetary reward maximization, rather than with (un)ethical behavior per se. In fact, using response times as a measure of the subject's reflection during the decision-making process, we can associate emotional arousal with the conflict between primary or instinctive and secondary or contemplative motivations and, more specifically, with deviations from the subject's pure monetary interest.

Centennial changes in solar activity and the response of galactic cosmic rays

There is a growing consensus that the eleven year modulation of galactic cosmic rays (GCRs) resulting from solar activity is related to interplanetary propagating diffusive barriers (PDBs). The source of these PDBs is not well understood and numerical models describing GCR modulation simulate their effect by scaling the diffusion tensor to the interplanetary magnetic field strength (IMF). The implications of a century-scale change in solar wind speed and open solar flux, for numerical modelling of GCR modulation and the reconstruction of GCR variations over the last hundred years are discussed. The dominant role of the solar non-axisymmetric magnetic field in both forcing longitudinal solar wind speed fluctuations at solar maximum and in increasing the IMF is discussed in the context of a long-term rise in the open solar magnetic flux.

The MELODIES project: integrating diverse data using Linked Data and cloud computing

We present an overview of the MELODIES project, which is developing new data-intensive environmental services based on data from Earth Observation satellites, government databases, national and European agencies and more. We focus here on the capabilities and benefits of the project’s “technical platform”, which applies cloud computing and Linked Data technologies to enable the development of these services, providing flexibility and scalability.

The dynamics and relationships of precipitation, temperature and convection boundaries in the dayside auroral ionosphere

A continuous band of high ion temperature, which persisted for about 8 h and zigzagged north-south across more than five degrees in latitude in the dayside (07:00– 15:00MLT) auroral ionosphere, was observed by the EISCAT VHF radar on 23 November 1999. Latitudinal gradients in the temperature of the F-region electron and ion gases (Te and Ti , respectively) have been compared with concurrent observations of particle precipitation and field-perpendicular convection by DMSP satellites, in order to reveal a physical explanation for the persistent band of high Ti , and to test the potential role of Ti and Te gradients as possible markers for the open-closed field line boundary. The north/south movement of the equatorward Ti boundary was found to be consistent with the contraction/expansion of the polar cap due to an unbalanced dayside and nightside reconnection. Sporadic intensifications in Ti , recurring on _10-min time scales, indicate that frictional heating was modulated by time-varying reconnection, and the band of high Ti was located on open flux. However, the equatorward Ti boundary was not found to be a close proxy of the open-closed boundary. The closest definable proxy of the open-closed boundary is the magnetosheath electron edge observed by DMSP. Although Te appears to be sensitive to magnetosheath electron fluxes, it is not found to be a suitable parameter for routine tracking of the open-closed boundary, as it involves case dependent analysis of the thermal balance. Finally, we have documented a region of newly-opened sunward convecting flux. This region is situated between the convection reversal boundary and the magnetosheath electron edge defining the openclosed boundary. This is consistent with a delay of several minutes between the arrival of the first (super-Alfv´enic) magnetosheath electrons and the response in the ionospheric convection, conveyed to the ionosphere by the interior Alfv´en wave. It represents a candidate footprint of the low-latitude boundary mixing layer on sunward convecting open flux