A critical role for ATF2 transcription factor in the regulation of E-selectin expression in response to non-endotoxin components of Neisseria meningitidis

Vascular injury is a serious complication of sepsis due to the gram-negative bacterium Neisseria meningitidis. One of the critical early steps in initiating this injury is via the interaction of leucocytes, particularly neutrophils, with adhesion molecules expressed on inflamed endothelium. We have previously demonstrated that both lipopolysaccharide (LPS) and non-LPS components of meningococci can induce very high levels of expression of the vascular endothelial cell adhesion molecule E-selectin, which is critical for early tethering and capture of neutrophils onto endothelium under flow. Using an LPS-deficient strain of meningococcus, we showed that very high levels of expression can be induced in primary endothelial cells, even in the context of weak activation of the major host signal transduction factor [nuclear factor-κB (NF-κB)]. In this study, we show that the particular propensity for N. meningitidis to induce high levels of expression is regulated at a transcriptional level, and demonstrate a significant role for phosphorylation of the ATF2 transcription factor, likely via mitogen-activated protein (MAP) kinases, on the activity of the E-selectin promoter. Furthermore, inhibition of E-selectin expression in response to the lpxA- strain by a p38 inhibitor indicates a significant role of a p38-dependent MAPK signalling pathway in ATF2 activation. Collectively, these data highlight the role that LPS and other bacterial components have in modulating endothelial function and their involvement in the pathogenesis of meningococcal sepsis. Better understanding of these multiple mechanisms induced by complex stimuli such as bacteria, and the specific inflammatory pathways they activate, may lead to improved, focused interventions in both meningococcal and potentially bacterial sepsis more generally

Wind Energy Resource Assessment of the Caribbean and Central America

A wind energy resource assessment of the Caribbean and Central America has identified many areas with good to outstanding wind resource potential for wind turbine applications. Annual average wind resource maps and summary tables have been developed for 35 island/country areas throughout the Caribbean and Central America region. The wind resource maps highlight the locations of major resource areas and provide estimates of the wind energy resource potential for typical well-exposed sites in these areas. The average energy in the wind flowing in the layer near the ground is expressed as a wind power class: the greater the average wind energy, the higher the wind power class. The summary tables that are included with each of the 35 island/country wind energy maps provide information on the frequency distribution of the wind speeds (expressed as estimates of the Weibull shape factor, k) and seasonal variations in the wind resource for the major wind resource areas identified on the maps. A new wind power class legend has been developed for relating the wind power classes to values of mean wind power density, mean wind speed, and Weibull k. Guidelines are presented on how to adjust these values to various heights above ground for different roughness and terrain characteristics. Information evaluated in preparing the assessment included existing meteorological data from airports and other weather stations, and from ships and buoys in offshore and coastal areas. In addition, new data from recent measurement sites established for wind energy siting studies were obtained for a few areas of the Caribbean. Other types of information evaluated in the assessment were climatological data and maps on winds aloft, surface pressure, air flow, and topography. The various data were screened and evaluated for their usefulness in preparing the wind resource assessment. Much of the surface data from airports and other land-based weather stations were determined to be from sheltered sites and were thus not very useful in assessing the wind resource at locations that are well exposed to the winds. Ship data were determined to be the most useful for estimating the large-scale wind flow and assessing the spatial distribution of the wind resource throughout the region. Techniques were developed for analyzing and correcting ship wind data and extrapolating these data to coastal and inland areas by considering terrain influences on the large-scale wind flow. In areas where extrapolation of ship wind data was not entirely feasible, such as interior areas of Central America, other techniques were developed for estimating the wind flow and distribution of the wind resource. Through the application of the various innovative techniques developed for assessing the wind resource throughout the Caribbean and Central America region, many areas with potentially good to outstanding wind resource were identified that had not been previously recognized. In areas where existing site data were available from exposed locations, the measured wind resource was compared with the estimated wind resource that was derived using the assessment techniques. In most cases, there was good agreement between the measured wind resource and the estimated wind resource. This assessment project supported activities being pursued by the U.S. Committee for Renewable Energy Commerce and Trade (CORECT), the U.S. government's interagency program to assist in overseas marketing and promote renewable energy exports. An overall goal of the program is to improve U.S. competitiveness in the world renewable energy market. The Caribbean and Central America assessment, which is the first of several possible follow-on international wind energy resource assessments, provides valuable information needed by the U.S. wind energy industry to identify suitable wind resource areas and concentrate their efforts on these areas

Where do you go when your periods go?: A case-study examining secondary amenorrhea in a professional internationally-capped female soccer player through the lens of the sport nutritionist.

This case study follows a professional internationally capped female soccer player's two-year journey from eumenorrhea, through injury, to amenorrhea, and the challenges faced by the player and nutritionist. The two years are split into three sections: (1) longitudinal profiling of the player, (2) nutrition to support her return from injury, and (3) investigation into the observed secondary amenorrhea. The cause of amenorrhea was investigated through the assessment of energy availability via doubly labelled water, remote food photography, blood biomarkers and resting metabolic rate. Despite having secondary amenorrhea and anovulatory cycles, the player did not have low energy availability. This study shows the importance for practitioner's, particularly nutritionists, to not assume that all menstrual irregularities are caused by low energy availability and could be caused by a combination of factors (e.g. clinical, physiological, and psychological), which requires a multi-disciplinary investigation and intervention team. This study also showed that education needs to be provided about menstrual health to elite female soccer players as the player (i) believed that not having a period was beneficial for performance and unsure of possible health implications; (ii) was convinced that a one-day bleed indicated a regular menstrual cycle; and (iii) was reluctant to waste the practitioners time discussing menstrual issues and was nervous of finding out if she had an actual health issue. It is therefore crucial that players feel comfortable in discussing their menstrual status with practitioners to support their performance and long-term health

Dynamic modeling of mean-reverting spreads for statistical arbitrage

Statistical arbitrage strategies, such as pairs trading and its generalizations, rely on the construction of mean-reverting spreads enjoying a certain degree of predictability. Gaussian linear state-space processes have recently been proposed as a model for such spreads under the assumption that the observed process is a noisy realization of some hidden states. Real-time estimation of the unobserved spread process can reveal temporary market inefficiencies which can then be exploited to generate excess returns. Building on previous work, we embrace the state-space framework for modeling spread processes and extend this methodology along three different directions. First, we introduce time-dependency in the model parameters, which allows for quick adaptation to changes in the data generating process. Second, we provide an on-line estimation algorithm that can be constantly run in real-time. Being computationally fast, the algorithm is particularly suitable for building aggressive trading strategies based on high-frequency data and may be used as a monitoring device for mean-reversion. Finally, our framework naturally provides informative uncertainty measures of all the estimated parameters. Experimental results based on Monte Carlo simulations and historical equity data are discussed, including a co-integration relationship involving two exchange-traded funds.Comment: 34 pages, 6 figures. Submitte

Properties of Blood, Porphyrins, and Exposure to Legacy and Emerging Persistent Organic Pollutants in Surf Scoters (Melanitta perspicillata) Overwintering on the South Coast of British Columbia, Canada

The surf scoter (Melanitta perspicillata) is a little-studied species of North American sea duck. Estimates suggest it has experienced a precipitous decline in breeding numbers over the latter half of the past century. To investigate the potential role of contaminant uptake and toxicity in the population decline, this study undertook to measure blood chemistry, porphyrin concentrations, EROD, and organic contaminants in mature surf scoters wintering in the Strait of Georgia, BC, Canada. Hepatic organochlorine pesticide, polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran, polychlorinated biphenyl (PCB), polybrominated diphenyl ether, and nonylphenol concentrations were relatively low; for example, ΣTEQs (toxic equivalents) for PCBs, dioxins, and furans combined ranged from 4.7 ng/kg wet weight in reference-site (Baynes Sound) birds to 11.4 ng/kg wet weight in birds from Vancouver Harbour. Nonetheless, elevated EROD activity indicated that birds in Howe Sound were responding to an Ah-receptor-mediated stressor, which was also affecting hematocrit values and possibly vitamin A status. In addition, a low proportion of lymphocytes in individuals across locations in early spring samples was associated with poor body condition. The apparent loss of fitness just prior to the onset of northerly migrations to breeding grounds is of particular concern. Compromised health of mature birds at this point in the season might impact negatively on the productivity and survival of some individuals, particularly those overwintering in Howe Sound

The development of path integration: combining estimations of distance and heading

Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

Super-Aggregations of Krill and Humpback Whales in Wilhelmina Bay, Antarctic Peninsula

Ecological relationships of krill and whales have not been explored in the Western Antarctic Peninsula (WAP), and have only rarely been studied elsewhere in the Southern Ocean. In the austral autumn we observed an extremely high density (5.1 whales per km2) of humpback whales (Megaptera novaeangliae) feeding on a super-aggregation of Antarctic krill (Euphausia superba) in Wilhelmina Bay. The krill biomass was approximately 2 million tons, distributed over an area of 100 km2 at densities of up to 2000 individuals m−3; reports of such ‘super-aggregations’ of krill have been absent in the scientific literature for >20 years. Retentive circulation patterns in the Bay entrained phytoplankton and meso-zooplankton that were grazed by the krill. Tagged whales rested during daylight hours and fed intensively throughout the night as krill migrated toward the surface. We infer that the previously unstudied WAP embayments are important foraging areas for whales during autumn and, furthermore, that meso-scale variation in the distribution of whales and their prey are important features of this system. Recent decreases in the abundance of Antarctic krill around the WAP have been linked to reductions in sea ice, mediated by rapid climate change in this area. At the same time, baleen whale populations in the Southern Ocean, which feed primarily on krill, are recovering from past exploitation. Consideration of these features and the effects of climate change on krill dynamics are critical to managing both krill harvests and the recovery of baleen whales in the Southern Ocean

Enhanced Visual Temporal Resolution in Autism Spectrum Disorders

Cognitive functions that rely on accurate sequencing of events, such as action planning and execution, verbal and nonverbal communication, and social interaction rely on well-tuned coding of temporal event-structure. Visual temporal event-structure coding was tested in 17 high-functioning adolescents and adults with autism spectrum disorder (ASD) and mental- and chronological-age matched typically-developing (TD) individuals using a perceptual simultaneity paradigm. Visual simultaneity thresholds were lower in individuals with ASD compared to TD individuals, suggesting that autism may be characterised by increased parsing of temporal event-structure, with a decreased capability for integration over time. Lower perceptual simultaneity thresholds in ASD were also related to increased developmental communication difficulties. These results are linked to detail-focussed and local processing bias