Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal raman spectroscopy

The stratum corneum (SC) barrier typically consists of layers of corneocytes embedded in a lipid continuum that regulates barrier function. The lipid domain containing ceramides, cholesterol, and free fatty acids provides the major pathway for most drugs permeating across SC. Penetration enhancers diminish the SC barrier function. The classic enhancer is dimethyl sulfoxide (DMSO). Its mechanisms of action remain unclear, although DMSO disrupts lipid organisation and may displace protein-bound water. Here we use confocal Raman spectroscopy to probe molecular interactions between a finite (depleting) dose of DMSO and SC, as functions of depth and time, providing novel information about residence time and location of DMSO in human SC in vivo

Reactions to peripheral image motion using a head/eye platform

The authors demonstrate four real-time reactive responses to movement in everyday scenes using an active head/eye platform. They first describe the design and realization of a high-bandwidth four-degree-of-freedom head/eye platform and visual feedback loop for the exploration of motion processing within active vision. The vision system divides processing into two scales and two broad functions. At a coarse, quasi-peripheral scale, detection and segmentation of new motion occurs across the whole image, and at fine scale, tracking of already detected motion takes place within a foveal region. Several simple coarse scale motion sensors which run concurrently at 25 Hz with latencies around 100 ms are detailed. The use of these sensors are discussed to drive the following real-time responses: (1) head/eye saccades to moving regions of interest; (2) a panic response to looming motion; (3) an opto-kinetic response to continuous motion across the image and (4) smooth pursuit of a moving target using motion alone.

Characterization of a Listeria monocytogenes Scott A isolate with high tolerance towards high hydrostatic pressure

An isolate of L. monocytogenes Scott A that is tolerant to high hydrostatic pressure (HHP), named AK01, was isolated upon a single pressurization treatment of 400 MPa for 20 min and was further characterized. The survival of exponential- and stationary-phase cells of AK01 in ACES [N-(2-acetamido)-2-aminoethanesulfonic acid] buffer was at least 2 log units higher than that of the wild type over a broad range of pressures (150 to 500 MPa), while both strains showed higher HHP tolerance (piezotolerance) in the stationary than in the exponential phase of growth. In semiskim milk, exponential-phase cells of both strains showed lower reductions upon pressurization than in buffer, but again, AK01 was more piezotolerant than the wild type. The piezotolerance of AK01 was retained for at least 40 generations in rich medium, suggesting a stable phenotype. Interestingly, cells of AK01 lacked flagella, were elongated, and showed slightly lower maximum specific growth rates than the wild type at 8, 22, and 30°C. Moreover, the piezotolerant strain AK01 showed increased resistance to heat, acid, and H2O2 compared with the wild type. The difference in HHP tolerance between the piezotolerant strain and the wild-type strain could not be attributed to differences in membrane fluidity, since strain AK01 and the wild type had identical in situ lipid melting curves as determined by Fourier transform infrared spectroscopy. The demonstrated occurrence of a piezotolerant isolate of L. monocytogenes underscores the need to further investigate the mechanisms underlying HHP resistance of food-borne microorganisms, which in turn will contribute to the appropriate design of safe, accurate, and feasible HHP treatments.

Accounting for the economic risk, caused by variation in disease severity, in fungicide dose decisions: exemplified for Mycosphaerella graminicola on winter wheat

A method is presented to calculate economic optimum fungicide doses accounting for the risk-aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost, plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimises net costs on average across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept ‘high loss’ years one year in ten or one year in twenty (i.e. specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk-aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over three years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of ‘high loss’ years requires substantially higher doses to be applied to all crops. Disease resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

A unified neurofuzzy model for classification

This work proposes a unified neurofuzzy modelling scheme. To begin with, the initial fuzzy base construction method is based on fuzzy clustering utilising a Gaussian mixture model (GMM) combined with the analysis of covariance (ANOVA) decomposition in order to obtain more compact univariate and bivariate membership functions over the subspaces of the input features. The mean and covariance of the Gaussian membership functions are found by the expectation maximisation (EM) algorithm with the merit of revealing the underlying density distribution of system inputs. The resultant set of membership functions forms the basis of the generalised fuzzy model (GFM) inference engine. The model structure and parameters of this neurofuzzy model are identified via the supervised subspace orthogonal least square (OLS) learning. Finally, instead of providing deterministic class label as model output by convention, a logistic regression model is applied to present the classifier’s output, in which the sigmoid type of logistic transfer function scales the outputs of the neurofuzzy model to the class probability. Experimental validation results are presented to demonstrate the effectiveness of the proposed neurofuzzy modelling scheme.

Climate change scenarios for precipitation extremes in Portugal

Precipitation indices are commonly used as climate change indicators. Considering four Climate Variability and Predictability-recommended indices, this study assesses possible changes in their spatial patterns over Portugal under future climatic conditions. Precipitation data from the regional climate model Consortium for Small-Scale Modelling–Climate version of the Local Model (CCLM) ensemble simulations with ECHAM5/MPI-OM1 boundary conditions are used for this purpose. For recent–past, medians and probability density functions of the CCLM-based indices are validated against station-based and gridded observational dataset from ENSEMBLES-based (gridded daily precipitation data provided by the European Climate Assessment & Dataset project) indices. It is demonstrated that the model is able to realistically reproduce not only precipitation but also the corresponding extreme indices. Climate change projections for 2071–2100 (A1B and B1 SRES scenarios) reveal significant decreases in total precipitation, particularly in autumn over northwestern and southern Portugal, though changes exhibit distinct local and seasonal patterns and are typically stronger for A1B than for B1. The increase in winter precipitation over northeastern Portugal in A1B is the most important exception to the overall drying trend. Contributions of extreme precipitation events to total precipitation are also expected to increase, mainly in winter and spring over northeastern Portugal. Strong projected increases in the dry spell lengths in autumn and spring are also noteworthy, giving evidence for an extension of the dry season from summer to spring and autumn. Although no coupling analysis is undertaken, these changes are qualitatively related to modifications in the large-scale circulation over the Euro-Atlantic area, more specifically to shifts in the position of the Azores High and associated changes in the large-scale pressure gradient over the area.

Radiative-dynamical climatology of the first-generation Canadian middle atmosphere model

The Canadian Middle Atmosphere Modelling (MAM) project is a collaboration between thé Atmospheric Environment Service (AES) of Environment Canada and several Canadian universities. Its goal is thé development of a comprehensive General Circulation Model of the troposphere-stratosphere-mesosphere System, starting from the AES/CCCma third-generation atmospheric General Circulation Model. This paper describes the basic features of the first-generation Canadian MAM and some aspects of its radiative-dynamical climatology. Standard first-order mean diagnostics are presented for monthly means and for the annual cycle of zonal-mean winds and temperatures. The mean meridional circulation is examined, and comparison is made between thé steady diabatic, downward controlled, and residual stream functions. It is found that downward control holds quite well in the monthly mean through most of the middle atmosphere, even during equinoctal periods. The relative roles of different drag processes in determining the mean downwelling over the wintertime polar middle stratosphere is examined, and the vertical structure of the drag is quantified.

Performance analysis of MIMO MRC in 3D mobile-to-mobile double-correlated channels

In this paper, we consider multiple-input multiple- output (MIMO) maximal ratio combining (MRC) systems and assess the system performance in terms of average symbol error probability (SEP), outage probability and ergodic capacity in double-correlated Rayleigh-and-Lognormal fading channels. In order to derive the receive and transmit correlation functions needed for the performance analysis, a three-dimensional (3D) MIMO mobile-to-mobile (M-to-M) channel model, which takes into account the effects of fast fading and shadowing is used. Numerical results are provided to show the effects of system parameters, such as maximum elevation angle of scatterers, orientation angle of antenna array in the x-y plane, angle between x-y plane and the antenna array orientation, and degree of scattering in the x-y plane, on the system performance.

Atmosphere drives recent interannual variability of the Atlantic meridional overturning circulation at 26.5°N

The RAPID-MOCHA array has observed the Atlantic Meridional overturning circulation (AMOC) at 26.5°N since 2004. During 2009/2010, there was a transient 30% weakening of the AMOC driven by anomalies in geostrophic and Ekman transports. Here, we use simulations based on the Met Office Forecast Ocean Assimilation Model (FOAM) to diagnose the relative importance of atmospheric forcings and internal ocean dynamics in driving the anomalous geostrophic circulation of 2009/10. Data assimilating experiments with FOAM accurately reproduce the mean strength and depth of the AMOC at 26.5°N. In addition, agreement between simulated and observed stream functions in the deep ocean is improved when we calculate the AMOC using a method that approximates the RAPID observations. The main features of the geostrophic circulation anomaly are captured by an ensemble of simulations without data-assimilation. These model results suggest that the atmosphere played a dominant role in driving recent interannual variability of the AMOC.

On the radius of centrality in evolving communication networks

In this article, we investigate how the choice of the attenuation factor in an extended version of Katz centrality influences the centrality of the nodes in evolving communication networks. For given snapshots of a network, observed over a period of time, recently developed communicability indices aim to identify the best broadcasters and listeners (receivers) in the network. Here we explore the attenuation factor constraint, in relation to the spectral radius (the largest eigenvalue) of the network at any point in time and its computation in the case of large networks. We compare three different communicability measures: standard, exponential, and relaxed (where the spectral radius bound on the attenuation factor is relaxed and the adjacency matrix is normalised, in order to maintain the convergence of the measure). Furthermore, using a vitality-based measure of both standard and relaxed communicability indices, we look at the ways of establishing the most important individuals for broadcasting and receiving of messages related to community bridging roles. We compare those measures with the scores produced by an iterative version of the PageRank algorithm and illustrate our findings with two examples of real-life evolving networks: the MIT reality mining data set, consisting of daily communications between 106 individuals over the period of one year, a UK Twitter mentions network, constructed from the direct \emph{tweets} between 12.4k individuals during one week, and a subset the Enron email data set.

The importance of the volatility risk premium for volatility forecasting

In this paper, we study the role of the volatility risk premium for the forecasting performance of implied volatility. We introduce a non-parametric and parsimonious approach to adjust the model-free implied volatility for the volatility risk premium and implement this methodology using more than 20 years of options and futures data on three major energy markets. Using regression models and statistical loss functions, we find compelling evidence to suggest that the risk premium adjusted implied volatility significantly outperforms other models, including its unadjusted counterpart. Our main finding holds for different choices of volatility estimators and competing time-series models, underlying the robustness of our results.

Microbes central to human reproduction

As studies uncover the breadth of microbes associated with human life, opportunities will emerge to manipulate and augment their functions in ways that improve health and longevity. From involvement in the complexities of reproduction and fetal/infant development, to delaying the onset of disease, and indeed countering many maladies, microbes offer hope for human well-being. Evidence is emerging to suggest that microbes may play a beneficial role in body sites traditionally viewed as being sterile. Although further evidence is required, we propose that much of medical dogma is about to change significantly through recognition and understanding of these hitherto unrecognized microbe–host interactions. A meeting of the International Scientific Association for Probiotics and Prebiotics held in Aberdeen, Scotland (June 2014), presented new views and challenged established concepts on the role of microbes in reproduction and health of the mother and infant. This article summarizes some of the main aspects of these discussions.

Reconnection at the high-latitude magnetopause during northward interplanetary magnetic field conditions

The Polar spacecraft had a prolonged encounter with the high-latitude dayside magnetopause on May 29, 1996. This encounter with the magnetopause occurred when the interplanetary magnetic field was directed northward. From the three-dimensional electron and ion distribution functions measured by the Hydra instrument, it has been possible to identify nearly all of the distinct boundary layer regions associated with high-latitude reconnection. The regions that have been identified are (1) the cusp; (2) the magnetopause current layer; (3) magnetosheath field lines that have interconnected in only the Northern Hemisphere; (4) magnetosheath field lines that have interconnected in only the Southern Hemisphere; (5) magnetosheath field lines that have interconnected in both the Northern and Southern Hemispheres; (6) magnetosheath that is disconnected from the terrestrial magnetic field; and (7) high-latitude plasma sheet field lines that are participating in magnetosheath reconnection. Reconnection over this time period was occurring at high latitudes over a broad local-time extent, interconnecting the magnetosheath and lobe and/or plasma sheet field lines in both the Northern and Southern Hemispheres. Newly closed boundary layer field lines were observed as reconnection occur-red first at high latitudes in one hemisphere and then later in the other. These observations establish the location of magnetopause reconnection during these northward interplanetary magnetic field conditions as being at high latitudes, poleward of the cusp, and further reinforce the general interpretation of electron and ion phase space density signatures as indicators of magnetic reconnection and boundary layer formation.

Regulation of cardiac myocyte cell death.

Cardiac myocyte death, whether through necrotic or apoptotic mechanisms, is a contributing factor to many cardiac pathologies. Although necrosis and apoptosis are the widely accepted forms of cell death, they may utilize the same cell death machinery. The environment within the cell probably dictates the final outcome, producing a spectrum of response between the two extremes. This review examines the probable mechanisms involved in myocyte death. Caspases, the generally accepted executioners of apoptosis, are significant in executing cardiac myocyte death, but other proteases (e.g., calpains, cathepsins) also promote cell death, and these are discussed. The two principal cell death pathways (death receptor- and mitochondrial-mediated) are described in relation to the emerging structural information for the principal proteins, and they are discussed relative to current understanding of myocyte cell death mechanisms. Whereas the mitochondrial pathway is probably a significant factor in myocyte death in both acute and chronic phases of myocardial diseases, the death receptor pathway may prove significant in the longer term. The Bcl-2 family of proteins are key regulators of the mitochondrial death pathway. These proteins are described and their possible functions are discussed. The commitment to cell death is also influenced by protein kinase cascades that are activated in the cell. Whereas certain pathways are cytoprotective (e.g., phosphatidylinositol 3'-kinase), the roles of other kinases are less clear. Since myocyte death is implicated in a number of cardiac pathologies, attenuation of the death pathways may prove important in ameliorating such disease states, and possible therapeutic strategies are explored.

On the parameterization of turbulent surface fluxes over heterogeneous sea ice surfaces

Turbulent surface fluxes of momentum and sensible and latent heat as well as surface temperature, air temperature, air humidity, and wind speed were measured by the German Falcon research aircraft over the marginal ice zone (MIZ) of the northern Baltic Sea and the Fram Strait. Applying the bulk formulas and the stability functions to the measurements, the roughness lengths for momentum z0, sensible heat zT, and latent heat zq were calculated. As mean values over a wide range of sea ice conditions, we obtain z0 = 5 � 10�4 m, zT = 1 � 10�8 m, and zq = 1 � 10�7 m. These correspond to the following mean values (± standard deviations) of neutral transfer coefficients reduced to 10 m height, CDN10 = (1.9 ± 0.8) � 10�3, CHN10 = (0.9 ± 0.3) � 10�3, and CEN10 = (1.0 ± 0.2) � 10�3. An average ratio of z0/zT � 104 was observed over the range of 10�6 m < z0 < 10�2 m and differs from previously published results over compact sea ice (10�1 < z0/zT < 103). Other observational results over heterogeneous sea ice do not exist. However, our z0/zT ratio approximately agrees with observations over heterogeneous land surfaces. Flux parameterizations based on commonly used roughness lengths ratios (z0 = zT = zq) overestimate the surface heat fluxes compared to our measurements by more than 100%.