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The opening of the Arctic presents opportunities for expanded natural resource extraction and increased shipping, both requiring substantial port development to facilitate safe and effective operat...

In the search for an understanding of how genetic variation contributes to the heritability of common human disease, the potential role of epigenetic factors, such as methylation, is being explored with increasing frequency. Although standard analyses test for associations between methylation levels at individual cytosine-phosphate-guanine (CpG) sites and phenotypes of interest, some investigators have begun testing for methylation and how methylation may modulate the effects of genetic polymorphisms on phenotypes. In our analysis, we used both a genome-wide and candidate gene approach to investigate potential single-nucleotide polymorphism (SNP)–CpG interactions on changes in triglyceride levels. Although we were able to identify numerous loci of interest when using an exploratory significance threshold, we did not identify any significant interactions using a strict genome-wide significance threshold. We were also able to identify numerous loci using the candidate gene approach, in which we focused on 18 genes with prior evidence of association of triglyceride levels. In particular, we identified GALNT2 loci as containing potential CpG sites that moderate the impact of genetic polymorphisms on triglyceride levels. Further work is needed to provide clear guidance on analytic strategies for testing SNP–CpG interactions, although leveraging prior biological understanding may be needed to improve statistical power in data sets with smaller sample sizes.

Standard tissue preparation for light and scanning electron microscopy (SEM) uses ethanol as a dehydrating agent but that can also dissolve cholesterol crystals (CC) leaving behind empty tissue imprints or "clefts". Cholesterol crystals may contribute to plaque rupture by their sharp tips that can tear membranes and trigger inflammation. Therefore, use of ethanol in tissue processing can mask the pathological role of CC. Here we evaluated the amount of cholesterol dissolved from CC with single and complete series of standard graded ethanol concentrations (25-100%) used in tissue preparation. Also, solubility of CC in ethanol at physiological levels was measured. Furthermore, we compared the effect of ethanol on CC in fresh human atherosclerotic plaques to matched segments dehydrated using vacuum (-1 atm, 12h). Tissue crystal density ranging from 0 to +3 was measured semi-quantitatively by SEM. For CC exposed to 25% and 100% ethanol for 10 min each, 0.38% and 95% of CC were dissolved respectively. Also, increase in CC solubility was significant at physiological levels of ethanol (0.16%) compared to water (43.4 ± 18.0 ng/mL vs. 30.9 ± 13.9 ng/mL; p

Contrail statistical prediction methods are often location specific. To take advantage of the fact that the upper-tropospheric (UT) meteorological conditions that favor “clear-sky outbreaks” of persisting contrails, or contrail favored areas (CFAs), tend to be synoptic in scale, a visual UT-map technique to hindcast CFAs has been developed and tested for subregions of the contiguous United States (CONUS) that have high outbreak frequencies in midseason months (January, April, July, and October) of 2000–02. The method compares daily maps with the composite fields for outbreak days (CON) versus nonoutbreak days (NON), and those assessments are evaluated using standard skill measures. Binary logistic regression determines which UT variables are significant predictors, individually and in combination. The reproducibility of the outbreak hindcast results is tested on the same subregions for the corresponding months of 2008–09. The results confirm the importance of UT relative humidity and vertical-motion (omega) map patterns in regional clear-sky outbreaks. Although the hindcast skill is modest, sensitivity tests suggest that the method will be substantially improved when a longer-term climatological dataset of outbreaks becomes available (to increase sample sizes) and with explicit consideration of the synoptic types on CON days. The latter is demonstrated specifically for the southern CONUS in January, where to improve hindcast success one should also consider the vertical wind shear in the upper troposphere, given the importance of the subtropical jet stream in contrail outbreaks there. Further development of the method to improve its skill ultimately should permit its use in combination with existing objective (statistical and physical models) methods of contrail prediction.

A carer or teacher often plays the role of proxy or spokesperson for a person living with an intellectual disability or form of cognitive or sensory impairment. Our research undertook co-design with people living with cognitive and sensory impairments and their proxies in order to explore new ways of facilitating communication. We developed simple functioning interactive prototypes to support people with a diverse range of competencies to communicate and explore their use. Deployment of the prototypes enabled use, appropriation and design after design by our two participant groups; adults living with cognitive or sensory impairments and children identified with language delays and autism spectrum disorder. The prototypes supported concrete expression of likes, dislikes, capabilities, emotional wants and needs and forms of expression that hitherto had not been fostered, further informing design. Carers and designers were surprised at the ways in which the technology was used and how it fostered new forms o...

Calcium phosphate biogenic materials are biocompatible and promote bioactivity and osteoconductivity, which implies their natural affinity and tendency to bond directly to bones subsequently replacing the host bone after implantation owing to its biodegradability. Calcium hydrogen phosphate dihydrate, CaHPO4·2H2O, is known to be a nucleation precursor, in aqueous solutions, for apatitic calcium phosphates and, hence, a potential starting material for bone substitutes. Numerous approaches, via hydrothermal and ambient synthetic routes, have been used to produce calcium phosphate from biogenic calcium carbonate, taking advantage of the peculiar architecture and composition of the latter. In this article, the lamellar region of the cuttlefish bone (Sepia officinalis) was used as a framework for the organized deposition of calcium phosphate crystals, at ambient conditions via a fast procedure involving an amorphous calcium carbonate intermediate, and ending with a conversion to calcium phosphate and a fixation procedure, thereby resulting in direct conversion of biogenic calcium carbonate into calcium phosphates at ambient conditions from the scale of months to hours.

Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy. These were correlated with inflammatory biomarkers, cardiac enzymes, % coronary stenosis, and Thrombolysis in Myocardial Infarction (TIMI) blush and flow grades. Crystals were detected in 254 patients (89%) and confirmed to be cholesterol by spectroscopy. Of 286 patients 240 (84%) had CCs compacted into clusters that were large enough to be measured and analyzed. Moderate to extensive CC content was present in 172 cases (60%). Totally occluded arteries had significantly larger CC clusters than partially occluded arteries (p 12,000 µm2 had significantly elevated interleukin-1 beta (IL-1β) levels (p

BODIPYs (Boron-dipyrromethene) and xanthoglows are two classes of fluorophores that can be derived from dipyrroles/dipyrrinones. Both BODIPY's and xanthoglows have a number of attributes that make them promising candidates as molecule probes such as large Stokes shifts, relatively high quantum yields, and the ability to be conjugated to molecules of interest. Additionally, these dyes are commonly used for the identification of analytes such as metals, lipids, and pesticides inside of living systems. This presentation describes synthetic strategies for constructing a u201chybridu201d xanthoglows/BODIPY molecule in order to create a more dynamic dye that shares characteristics of BODIPYu2019s and xanthoglows. This hybrid class of molecules, which are highly likely to be fluorescent, have never been previously synthesized or studied. In addition, we describe additional N,N-bridging groups that effectively replace the carbonyl-bridge of the xanthoglow unit.

The malaria infection is initiated in mammals by injection of the sporozoite stage of the parasite through the bite of Plasmodium-infected, female Anopheles mosquitoes. Sporozoites are injected into extravascular portions of the skin while the mosquito is probing for a blood source. Sporozoite gliding motility allows them to locate and penetrate blood vessels of the dermis or subcutaneous tissues; once in the blood, they reach the liver, within which they continue their development. Some of the injected parasites invade dermal lymph vessels and travel to the proximal draining lymphatic node, where they interact with host immunocytes. The host responds to viable or attenuated sporozoites with antibodies directed against the immunodominant circumsporozoite protein (CSP), as well as against other sporozoite proteins. These CSP antibodies can inhibit the numbers of sporozoites injected by mosquitoes and the motility of those injected into the skin. This first phase of the immune response is followed by cell-mediated immunity involving CD8 T-cells directed against the developing liver stage of the parasite. This review discusses the early history of imaging studies, and focuses on the role that imaging has played in enabling a better understanding of both the induction and effector functions of the immune responses against sporozoites.

Many cancers and atherosclerosis share similar risk factors. We have previously demonstrated that cholesterol crystals (CCs) activate production of interleukin-1 beta (IL-1β). A recent trial has demonstrated that an IL-1β inhibitor was associated with significant reduction in cardiovascular events

Supraglacial channels are an important mechanism for surface water transport over the ablation zone of western Greenland. The first assessment of the spatio-temporal distribution of surface melt channels and their relationship to supraglacial lakes over the Jakobshavn Isbrae region of Western Greenland was analysed using Landsat Enhanced Thematic Mapper Plus panchromatic images during the 2007 melt season. A total of 1188 melt channels were delineated and show an increase in the number of melt channels throughout the season, reaching a peak on 9 August. Water-filled melt channels advanced to a maximum elevation of 1647 m on 9 August and attained a minimum average slope of 0.009 on 8 July. The ablation zone demonstrates two hydrologic modes, where crevasse and moulin terminating channels dominate at elevations 800 m. Development of higher-order networks is interrupted by flow divergence due to partitioning of melt water into vertical infiltration through moulins and crevasse fields prevalent at lower elevations. Tributary and connector networks between 800 and 1200 m in elevation are correlated with fewer lake occurrences, lower surface velocities (~50 m a−1), and ice flow dominated by internal deformation over basal sliding. High-order channels are associated with lake basins that exceed melt water storage capacity. Evolution of channel networks is coupled to changes in melt water production, runoff, and ice dynamics with implication for the englacial and subglacial environments. © 2013 The Authors. Hydrological Processes Published by John Wiley & Sons, Ltd.

Many within the information field have declared that libraries, archives and museums (LAMs) must collaborate or else face extinction. The convergence of these institutions marks the extreme of this movement, which is currently being driven by technological initiatives that seek to attract new, digitally engaged users. This paper presents some recent initiatives to bring these institutions together and explores the history of exchange between LAMs. Finally, a more pointed examination of archives in museums provides grounds to question the ability of technology to facilitate deep-rooted collaboration. This reading of the history of LAMs and their current challenges raises a concern that convergence is nothing more than a rebranding exercise, in which archives appear vulnerable to lose their defining characteristics.

The spatial distribution of supraglacial lakes has been hypothesized to be dominantly controlled by the component of surface roughness influenced by basal topography. Basal topography and surface roughness profiles within the Jakobshavn Isbrae drainage basin in western Greenland, acquired from an ice-penetrating radar echo sounder, were analysed through fourier and wavelet decompositions. Spectral analyses of basal-to-surface transfer under a range of ice thickness were compared with spatial distribution of lakes mapped from high-resolution Landsat imagery. Fourier analysis identifies dominant signals in both the basal and surface profiles to be ranging between wavelengths of 1·25–12·5 km. The strongest peaks of transfer of basal signals to the surface were identified at wavelengths ∼11∼5 km. Wavelet analysis identifies these peaks with thicker (1200–1400 m) and thinner (500–700 m) ice respectively and also identifies surface frequencies not present in the basal signal indicating some influence from other factors. Spatial autocorrelation analysis of supraglacial lake distribution indentifies high correlations at 1·9, 5·6, 11, 24, and 30 km lags. Lags at 5·6 and 11 km correspond to dominant frequencies present in the basal and surface profiles over thinner and thicker ice respectively. These ∼5 and ∼11 km frequency components present in the basal topography, surface roughness, and lake distribution are within the theoretical transfer window of basal-to-surface transfer as a function of ice thickness. The transect analysed in this study does not contain wavelengths in the surface structure that are less than the ice thickness, even though there are relatively higher frequencies present in the surface profile between 0 and 15 km that have less power in the basal profile. Copyright © 2011 John Wiley & Sons, Ltd.

This study reports on an examination of the effectiveness of a reading intervention for adults with disabilities in a vocational rehabilitation setting. Participants were 57 adults with disabilities and low reading skills enrolled at the Reading Clinic at the Michigan Career and Technical Institute. As part of a 3-year research and demonstration grant evaluation project, participants received an individualized reading intervention that targeted phonological processing, orthographic pattern recognition, and comprehension for adults with disabilities and low reading levels. The particular program incorporated fluency exercises at every level of the structured, explicit, and systematic intervention curriculum. Results showed that participants made moderate to large gains in passage reading accuracy and comprehension during the course of the intervention. Gains in passage reading rate were not statistically significant. Results are discussed in relation to theories of reading disability and intervention for adults with reading disabilities in vocational rehabilitation settings.

Malaria infection is initiated when a mosquito injects Plasmodium sporozoites into a mammalian host. Sporozoites exhibit gliding motility both in vitro and in vivo. This motility is associated with the secretion of at least two proteins, circumsporozoite protein (CSP) and thrombospondin-related anonymous protein (TRAP). Both derive from micronemes, which are organelles that empty out of the apical end of the sporozoite. Sporozoite motility can be initiated in vitro by albumin added to the medium. To investigate how albumin functions in this process, we studied second messenger signalling within the sporozoite. Using pharmacological activators and inhibitors, we have concluded that gliding motility is initiated when albumin interacts with the surface of the sporozoite and that this leads to a signal transduction cascade within the sporozoite, including the elevation of intracellular cAMP, the modulation of sporozoite motility by Ca(2+) and the release of microneme proteins.

The number of malaria sporozoites delivered to a host by mosquitoes is thought to have a significant influence on the subsequent course of the infection in the mammalian host. We did studies with Anopheles stephensi mosquitoes with salivary gland infections of Plasmodium berghei sporozoites expressing a red fluorescent protein. After individual mosquitoes fed on an ear pinna or the ventral abdomen of a mouse, fluorescence microscopy was used to count numbers of sporozoites. Mosquitoes allowed to feed on the ear for periods of 3 versus 15 min deposited means of 281 versus 452 sporozoites, respectively, into the skin; this may have epidemiological implications because mosquitoes can feed for longer periods of time on sleeping hosts. Mosquitoes feeding on the ventral abdomen injected sporozoites not only into the skin but also into the underlying peritoneal musculature. Although mosquitoes injected fewer sporozoites into the abdominal tissues, more of these were reingested into the mosquito midgut, probably a consequence of easier access to blood intake from the abdominal area. The most consistent parameter of sporozoite transmission dynamics under all conditions of mosquito probing and feeding was the relatively slow release rate of sporozoites (∼1 to 2.5 per second) from the mosquito proboscis. The numbers of sporozoites introduced into the host by mosquitoes and the transmission efficiencies of sporozoite delivery are multifactorial phenomena that vary with length of probing time, skin site being fed upon, and numbers of sporozoites within the salivary glands.