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Intercalation in few-layer (2D) materials is a rapidly growing area of research to develop next-generation energy-storage and optoelectronic devices, including batteries, sensors, transistors, and electrically tunable displays. Identifying fundamental differences between intercalation in bulk and 2D materials will play a key role in developing functional devices. Herein, advances in few-layer intercalation are addressed in the historical context of bulk intercalation. First, synthesis methods and structural properties are discussed, emphasizing electrochemical techniques, the mechanism of intercalation, and the formation of a solid-electrolyte interphase. To address fundamental differences between bulk and 2D materials, scaling relationships describe how intercalation kinetics, structure, and electronic and optical properties depend on material thickness and lateral dimension. Here, diffusion rates, pseudocapacity, limits of staging, and electronic structure are compared for bulk and 2D materials. Next, the optoelectronic properties are summarized, focusing on charge transfer, conductivity, and electronic structure. For energy devices, opportunities also emerge to design van der Waals heterostructures with high capacities and excellent cycling performance. Initial studies of heterostructured electrodes are compared to state-of-the-art battery materials. Finally, challenges and opportunities are presented for 2D materials in energy and optoelectronic applications, along with promising research directions in synthesis and characterization to engineer 2D materials for superior devices.

Background. The Medicare Health Outcomes Survey (HOS), a nationwide annual survey of Medicare beneficiaries, includes the Centers for Disease Control and Prevention’s HRQOL-4 questionnaire and Veterans RAND 12-item Health Survey (VR-12). This study compared EQ-5D scores derived from the HRQOL-4 (dEQ-5D) to SF-6D scores derived from VR-12. Methods. Data were from Medicare HOS Cohort 15 (2012 baseline; 2014 follow-up). We included participants aged 65+ ( n = 105,473). We compared score distributions, evaluated known-groups validity, assessed each index as a predictor for mortality, and estimated quality-adjusted life years (QALYs) using the dEQ-5D and SF-6D. Results. Compared to the SF-6D, the dEQ-5D had a higher mean score (0.787 v. 0.691) and larger standard deviation (0.310 v. 0.101). The decreases in estimated scores associated with chronic conditions were greater for the dEQ-5D than for the SF-6D. For example, dEQ-5D scores for persons with depression decreased 0.456 points compared to 0.141 points for the SF-6D. The dEQ-5D strongly predicted mortality, as adjusted hazard ratios for the first to fourth quintiles, relative to the fifth quintile, were 2.2, 1.7, 1.8, and 1.5, respectively, while the association between SF-6D and mortality was weaker or nonexistent (adjusted hazard ratios were 1.3, 1.1, 1.0, and 0.6, respectively). Compared to the SF-6D, QALYs estimated using the dEQ-5D were higher overall (5.6 v. 4.9 years), higher for persons with less debilitating conditions (e.g., hypertension, 5.0 v. 4.4 years), and lower for more debilitating conditions (e.g. depression, 2.5 v. 2.8 years). Conclusions. Compared to the SF-6D, the dEQ-5D was better able to measure individuals’ overall health; detect the differential impact of chronic conditions, particularly among persons in poorer health; and predict mortality. The HRQOL-4 questionnaire may be valuable for monitoring and improving health outcomes for the Medical HOS data set.

Background The staging method for activities of daily living (ADLs) limitations developed by Stineman and colleagues that classifies people into five stages can reflect severity of activity limitations. Objective To assess the impact of stages of limitations in ADLs on quality-adjusted life years (QALYs) and the relative severity of each ADL limitation for a large, nationally-representative sample of the U.S. community-dwelling older population. Methods Data were obtained from the Limited Dataset of the Medicare Health Outcomes Survey Cohort 15 (2012 baseline survey, 2014 follow-up survey). We included respondents aged ≥65 years (n = 105,473). We estimated expected QALYs throughout the remaining lifetime of participants stratified by the ADL limitation status and stages of ADL limitations. Results Overall, the expected QALYs was 5.6 years. QALYs decreased with increasing stages of ADL limitations. The adjusted QALYs for Stage 0 (no limitation) participants were 6.8; for Stage I (mild) participants, 3.9; for Stage II (moderate) participants, 2.2; for Stage III (severe) participants, 1.8; and for Stage IV (complete limitations) participants, 1.5. Differences in QALYs occurred between individual ADL items within an ADL stage. In Stage I, for example, participants who reported only problems with getting in or out of chairs had 6.7 QALYs which was markedly higher than participants who reported only problems with walking (3.8 QALYs). Conclusions Our findings provide additional evidence that Stineman's ADL stages serve as valid estimates of the overall health of elderly Americans. Self-reported ADL status should be routinely collected as a patient-reported outcome in the elderly population.

Ocean acidification (OA) is predicted to alter benthic marine community structure and function, however, there is a paucity of field experiments in benthic soft sediment communities and ecosystems. Benthic diatoms are important components of Antarctic coastal ecosystems, however very little is known of how they will respond to ocean acidification. Ocean acidification conditions were maintained by incremental computer controlled addition of high fCO2 seawater representing OA conditions predicted for the year 2100. Respiration chambers and PAM fluorescence techniques were used to investigate acute behavioural, photosynthetic and net production responses of benthic microalgae communities to OA in in-situ field experiments. We demonstrate how OA can modify behavioural ecology, which changes photo-physiology and net production of benthic microalgae. Ocean acidification treatments significantly altered behavioural ecology, which in turn altered photo-physiology. The ecological trends presented here have the potential to manifest into significant ecological change over longer time periods.

Objective To test whether emergency contraception use in reproductive-aged cancer survivors is higher than in the general U.S. population and evaluate factors associated with use among survivors. Design A retrospective cohort study compared emergency contraception use between cancer survivors in the Reproductive Window Study on ovarian function after cancer and in the general population in the 2006–2010 National Survey for Family Growth. In a cross-sectional analysis of survivors, multivariable models were used to test associations between participant characteristics and emergency contraception use. Setting Not applicable. Patient(s) A total of 616 female cancer survivors aged 18–40. Intervention(s) None. Main Outcome Measure(s) Self-reported emergency contraception use. Result(s) The mean age of survivors was 33.4 ± 4.7, at a mean 7.5 years since diagnosis. Breast cancer (22%), Hodgkin lymphoma (18%), and leukemia (8%) were the most common cancers. Since diagnosis, 156 (25.3%) used emergency contraception, 60% because of not otherwise using contraception. Age-adjusted prevalence of use was higher in survivors than in the general population (28.3% [95% confidence interval (CI) 24.7–31.9] vs. 12.0% [95% CI 11.1–12.9]). In multivariable analysis among survivors, nonwhite race (prevalence ratio [PR] 1.3, 95% CI 1.0–1.8), breast cancer (PR 0.6, 95% CI 0.4–1.0), partnered relationship (PR 0.6, 95% CI 0.5–0.9), and older age (age 36–40 vs. 31–35; PR 0.7, 95% CI 0.5–1.0) were associated with emergency contraception. Conclusion(s) Female young adult cancer survivors were significantly more likely to use emergency contraception compared with the general population. Populations including nonwhite survivors have a higher risk, suggesting differences in family planning care. Strategies to improve contraception and decrease the need for emergency contraception are needed.

A Free Ocean Carbon Enrichment experiment that manipulates seawater pH on a coral reef flat shows that the level of ocean acidification at which net dissolution of corals occurs may arrive much sooner than expected.

Landscape heterogeneity impacts community assembly in animals and plants, but it is not clear if this ecological concept extends to microbes. To examine this question, we chose to investigate polar soil environments from the Antarctic and Arctic, where microbes often form the major component of biomass. We examined soil environments that ranged in connectivity from relatively well-connected slopes to patchy, fragmented landforms that comprised isolated frost boils. We found landscape connectedness to have a significant correlation with microbial community structure and connectivity, as measured by co-occurrence networks. Soils from within fragmented landforms appeared to exhibit less local environmental heterogeneity, harboured more similar communities, but fewer biological associations than connected landforms. This effect was observed at both poles, despite the geographical distances and ecological differences between them. We suggest that microbial communities inhabiting well-connected landscape elements respond consistently to regional-scale gradients in biotic and edaphic factors. Conversely, the repeated freeze thaw cycles that characterize fragmented landscapes create barriers within the landscape and act to homogenize the soil environment within individual frost boils and consequently the microbial communities. We propose that lower microbial connectivity in the fragmented landforms is a function of smaller patch size and continual disturbances following soil mixing.

An integrated analysis of biological and geoscientific data collected from the nearshore marine environment of the Vestfold Hills was used to identify benthic habitats and associated communities and examine relationships between benthic community composition and environmental characteristics. A 48 km2 area was surveyed using a multibeam echosounder system (MBES) to produce high-resolution bathymetry and backscatter intensity maps of the seabed. Epibenthic community data and in situ observations of substrate composition and seafloor bedforms and features were obtained from towed underwater video. A comparison of top-down and bottom-up approaches to defining benthic habitats was used to improve understanding of the applicability of mapping methodologies. On a broad scale, both approaches produced habitat classes distinguished largely by geomorphic features, with substrate and depth identified as the main controls of benthic community composition, however, the relationship between benthic community composition and environmental characteristics is complex with many variables contributing to differences in community composition. The top-down approach was based on geomorphic units defined using abiotic characteristics and the assemblages identified within the geomorphic were very broad with only weak distinction between assemblages. Conversely, the bottom-up approach generated additional habitat classes, identified clear defining taxa for each class, greater distinction between the benthic communities, and allowed identification of additional environmental factors (i.e. sea ice cover) that influence benthic community distribution that are not discernible from geomorphic information alone. The habitat types identified and mapped using the bottom-up approach include shallow boulder fields and exposed bedrock which are dominated by dense macroalgae communities, and steep slopes, muddy basins and sandy plains which are dominated by invertebrate communities. The results indicate that a bottom-up approach is preferable for benthic habitat mapping, however, where detailed information is not available, geomorphic information provides a reasonable indication of the distribution of benthic habitats and communities. This study highlights the utility of multibeam sonar for interpretation of seafloor morphology and substrate and the multibeam data provide a physical framework for understanding benthic habitats and the distribution of benthic communities. This research provides the scientific context and spatial framework for managing the Vestfold Hills nearshore marine environment and provides a baseline for assessing environmental change.

A survey of nearshore areas in the Vestfold Hills, Antarctica, using high-resolution multibeam swath bathymetry provided both a detailed digital bathymetric model and information on sediment acoustic backscatter. Combined with underwater video transects and sediment sampling, these data were used to identify and map geomorphic units. Six geomorphic units identified in the survey region include: rocky outcrops, basins, pediments, valleys, scarps and embayments. In addition to geomorphic units, the data revealed sedimentary features that provide insights into post-glacial sediment transport and erosion in the area. Ice keel pits and scours are common, and sea floor channels, scour depressions and sand ribbons indicate transport and deposition by wind-driven currents and oceanographic circulation. Gullies and sediment lobes observed on steep slopes indicate mass movement of sediment. Some of these processes have not been directly observed to date, but their effectiveness in shaping the modern sea floor is clearly indicated by the sea floor mapping data. The embayments preserve a mantle of boulder sand probably deposited by cold-based glaciers which were flanked by faster-flowing ice in adjoining regions.

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are, Highlights • A seven-miRNA panel (MELmiR-7) detected the presence of melanoma with high sensitivity (93%) and specificity (≥ 82%). • In serially collected stage IV specimens, members of the ‘MELmiR-7’ panel confirmed tumour progression in 100% of cases. • The ‘MELmiR-7’ panel is superior to currently used serological markers for melanoma progression, recurrence, and survival.

// Mitchell S. Stark 1,2 , Vanessa F. Bonazzi 3 , Glen M. Boyle 1 , Jane M. Palmer 1 , Judith Symmons 1 , Catherine M. Lanagan 1 , Christopher W. Schmidt 1 , Adrian C. Herington 2 , Robert Ballotti 3 , Pamela M. Pollock 2 and Nicholas K. Hayward 1 1 QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia 2 School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia 3 Inserm U1065, Centre Mediterraneen de Medecine Moleculaire, Equipe 1, Biologie et pathologies des melanocytes, Nice, France Correspondence to: Mitchell S. Stark, email: // Keywords : miRNA, microRNA, miR-514a, BRAFi, NF1 Received : March 16, 2015 Accepted : April 07, 2015 Published : April 23, 2015 Abstract To identify ‘melanoma-specific’ microRNAs (miRNAs) we used an unbiased microRNA profiling approach to comprehensively study cutaneous melanoma in relation to other solid malignancies, which revealed 233 differentially expressed (≥ 2 fold, p < 0.05) miRNAs. Among the top 20 most significantly different miRNAs was hsa-miR-514a-3p. miR-514a is a member of a cluster of miRNAs (miR-506-514) involved in initiating melanocyte transformation and promotion of melanoma growth. We found miR-514a was expressed in 38/55 (69%) melanoma cell lines but in only 1/34 (3%) other solid cancers. To identify miR-514a regulated targets we conducted a miR-514a-mRNA ‘pull-down’ experiment, which revealed hundreds of genes, including: CTNNB1 , CDK2 , MC1R , and NF1 , previously associated with melanoma. NF1 was selected for functional validation because of its recent implication inacquired resistance to BRAFV600E -targeted therapy. Luciferase-reporter assays confirmed NF1 as a direct target of miR-514a and over-expression of miR-514a in melanoma cell lines inhibited NF1 expression, which correlated with increased survival of BRAFV600E cells treated with PLX4032. These data provide another mechanism for the dysregulation of the MAPK pathway which may contribute to the profound resistance associated with current RAF-targeted therapies. Mitchell S. Stark

Human impacts threaten not only species, but also entire ecosystems. Ecosystems under stress can collapse or transition into different states, potentially reducing biodiversity at a variety of scales. Here we examine the vulnerability of Antarctic shallow invertebrate-dominated ecosystems, which may be threatened for several reasons.These unique shallow-water communities mostly consist of dark-adapted invertebrates, and rely on sea ice to create low-light marine environments. Climate change is likely to cause early breakout of seasonal sea ice in parts of Antarctica, which will dramatically increase the amount of light reaching shallow seabed. This is predicted to result in ecological regime shifts, in which invertebrate-dominated communities are replaced by macroalgal beds. Habitat for these endemic Antarctic ecosystems is globally rare, and the fragmented nature of their distribution along Antarctic coast increases their sensitivity to change. Concurrently, human activities in Antarctica are concentrated in areas where these habitats occur, compounding potential impacts. While there are clear mechanisms of threat to these ecosystems, lack of knowledge about their spatial distribution obscures predictions of potential ecosystem loss, and the likelihood of recovery. In this paper we describe these ecosystems, their association with the environment and the reasons for their vulnerability.We estimate their spatial distribution around Antarctica using sea ice and bathymetric data, and apply the International Union for Conservation of Nature Red List of Ecosystems criteria to assess their vulnerability. Best available data suggest that shallow ice-covered ecosystems are likely Near Threatened to Vulnerable in places, although the magnitude of risk is spatially variable and requires additional data to strengthen the assessment.

The melanoma transformation rate of an individual nevus is very low despite the detection of oncogenic BRAF or NRAS mutations in 100% of nevi. Acquired melanocytic nevi do, however, mimic melanoma, and approximately 30% of all melanomas arise within pre-existing nevi. Using whole-exome sequencing of 30 matched nevi, adjacent normal skin, and saliva we sought to identify the underlying genetic mechanisms for nevus development. All nevi were clinically, dermoscopically, and histopathologically documented. In addition to identifying somatic mutations, we found mutational signatures relating to UVR mirroring those found in cutaneous melanoma. In nevi we frequently observed the presence of the UVR mutation signature compared with adjacent normal skin (97% vs. 10%, respectively). Copy number aberration analysis showed that for nevi with copy number loss of tumor suppressor genes, this loss was balanced by loss of potent oncogenes. Moreover, reticular and nonspecific patterned nevi showed an increased (P0.0001) number of copy number aberrations compared with globular nevi. The mutation signature data generated in this study confirms that UVR strongly contributes to nevogenesis. Copy number changes reflect at a genomic level the dermoscopic differences of acquired melanocytic nevi. Finally, we propose that the balanced loss of tumor suppressor genes and oncogenes is a protective mechanism of acquired melanocytic nevi.

Summary The vector potential formulation is a promising solution method for nonlinear electromechanically coupled boundary value problems. However, one of the drawbacks of this formulation is the non-uniqueness of the (electric) vector potential in three dimensions. The present paper focuses on the Coulomb gauging method to overcome this problem. In particular, the corresponding gauging boundary conditions and their consistency with the physical boundary conditions are examined in detail. Furthermore, certain topological features like cavities and multiply connectedness of the domain of analysis are taken into account. Different variational/weak formulations being appropriate for finite element implementation are described. Finally, the suitability of these formulations is demonstrated in several numerical examples. Copyright © 2015 John Wiley & Sons, Ltd.

The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh-frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR-150-5p, miR-142-3p and miR-142-5p. Co-analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR-150-5p and the miR-142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets.

Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor genePTPRJin 19% of cases. NoBRAFmutations were detected, but activatingRASmutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes.MDM2amplifications (24%) andTP53mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen inBRAFwild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.AUTHOR SUMMARYMelanoma, an aggressive cancer arising from transformed melanocytes, commonly occurs in pet dogs. Unlike human melanoma, which most often occurs in sun-exposed cutaneous skin, canine melanoma typically arises in sun-shielded oral mucosa. Clinical features of canine melanoma resemble those of human melanoma, particularly the less common sun-shielded human subtypes. However, whereas the genomic basis of diverse human melanoma subtypes is well understood, canine melanoma genomics remain poorly defined. Similarly, although diverse new treatments for human melanoma based on a biologic disease understanding have recently shown dramatic improvements in outcomes for these patients, treatments for canine melanoma are limited and outcomes remain universally poor. Detailing the genomic basis of canine melanoma thus provides untapped potential for improving the lives of pet dogs while also helping to establish canine melanoma as a comparative model system for informing human melanoma biology and treatment. In order to better define the genomic landscape of canine melanoma, we performed multi-platform characterization of 37 tumors. Our integrated analysis confirms that these tumors commonly contain mutations in canine orthologs of human cancer genes such asRAS,MDM2, andTP53as well mutational patterns that share important similarities with human melanoma subtypes. We have also found a new putative cancer gene,PTPRJ, frequently mutated in canine melanoma. These data will guide additional biologic and therapeutic studies in canine melanoma while framing the utility of comparative studies of canine and human cancers more broadly.

Melanoma is a complex multifactorial disease; therefore, a combination of various approaches is necessary to girt all aspects of its biology and identify the many different genes and factors involved in its etiology.Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. Here, we describe a new pipeline based on an integrative and comparative analysis of several array platform, post-demethylation treatment expression data, methylation array, and constitutive mRNA expression analysis to identify novel TSGs frequently methylated in melanoma.

Acquired naevi can have unique dermoscopic patterns that correspond to distinct microanatomical growth patterns. Previous studies on acquired naevi stratified according to dermoscopic pattern focused on the frequency of somatic BRAF mutations, whereas NRAS mutations remained to be elucidated.To investigate the BRAF and NRAS mutation prevalence and activation of the mitogen-activated protein kinase (MAPK) pathway in distinct dermoscopic subtypes of acquired naevi.Common mutations present in BRAF and NRAS were assessed in 40 globular, reticular and peripheral rim of globules (PG) subtypes of acquired naevi from 27 participants (19 male, 8 female; mean age 46·7 years) selected from 1261 eligible volunteers. Mutations were determined using the highly sensitive and quantitative QX200 droplet digital™ polymerase chain reaction (ddPCR) system.The BRAF V600E (c.1799TA or c.1799_1800delTGinsA) and BRAF V600K mutations were detected in 85% (n = 34/40) of naevi. All BRAF wild-type naevi (15%; n = 6/40) harboured an NRAS codon 12/13 or 61 mutation. BRAF mutations were present in 92% (n = 12/13) of globular and 100% (n = 12/12) of PG naevi, whereas reticular naevi were 67% (n = 10/15) BRAF- and 33% (n = 5/15) NRAS-mutant (P = 0·037).We discovered that 100% of the assessed acquired naevi had either a BRAF or NRAS mutation. Using sensitive techniques capable of single-cell mutation detection, it is likely that all acquired naevi will be mutated for BRAF or NRAS. Because both of these mutations are prevalent in distinct dermoscopic naevus subsets, our study supports the role of the MAPK pathway in the development of benign melanocytic proliferations, indicating that additional genomic events besides somatic mutations in BRAF or NRAS are required for melanoma development.

A shoreline waste disposal site at Casey Station, Antarctica was removed because it was causing impacts in the adjacent marine environment (Brown Bay). We conducted a field experiment to determine whether the excavation created further impacts. Trays of clean, defaunated sediment were deployed at two locations within Brown Bay and two control locations, two years prior to remediation. Trays were sampled one year before, 1 month before, 1 month after and two years after the excavation. An increase in metals was found at Brown Bay two years after the remediation. However there was little evidence of impacts on sediment assemblages. Communities at each location were different, but differences from before to after the remediation were comparable, indicating there were unlikely to have been further impacts. We demonstrate that abandoned waste disposal sites in hydrologically active places in Antarctica can be removed without creating greater adverse impacts to ecosystems downstream.

During the 2009/2010 summer, a comprehensive environmental impact assessment (EIA) of the wastewater discharge at Davis Station, East Antarctica was completed. As part of this, histological alteration of gill and liver tissue in Antarctic Rock-cod (Trematomus bernacchii) from four sites along a spatial gradient from the wastewater outfall were assessed. All fish within 800 m of the outfall exhibited significant histological changes in both tissues. Common pathologies observed in fish closest to the outfall include proliferation of epithelial cells with associated secondary lamellar fusion in the gills and multifocal granulomata with inflammation and necrosis as well as cysts in the liver. Fish from sites >800 m from the outfall also exhibited alterations but to a lesser degree, with prevalence and severity decreasing with increasing distance from the outfall. This study highlights the value of histopathological investigations as part of EIAs and provides the first evidence of sub-lethal alteration associated with wastewater discharge in East Antarctica.

Wastewater containing human sewage is often discharged with little or no treatment into the Antarctic marine environment. Faecal sterols (primarily coprostanol) in sediments have been used for assessment of human sewage contamination in this environment, butin situproduction and indigenous faunal inputs can confound such determinations. Using gas chromatography with mass spectral detection profiles of both C27and C29sterols, potential sources of faecal sterols were examined in nearshore marine sediments, encompassing sites proximal and distal to the wastewater outfall at Davis Station. Faeces from indigenous seals and penguins were also examined. Faeces from several indigenous species contained significant quantities of coprostanol but not 24-ethylcoprostanol, which is present in human faeces.In situcoprostanol and 24-ethylcoprostanol production was identified by co-production of their respectiveepi-isomers at sites remote from the wastewater source and in high total organic matter sediments. A C29sterols-based polyphasic likelihood assessment matrix for human sewage contamination is presented, which distinguishes human from local fauna faecal inputs andin situproduction in the Antarctic environment. Sewage contamination was detected up to 1.5 km from Davis Station.

The effect of low concentrations of methyl linoleate on the autoxidation of squalane (2, 6, 10, 15, 19, 23 hexamethyltetracosane) was investigated at temperatures 100 to 170 °C as a chemical model of the effect of biodiesel on the degradation of hydrocarbon lubricants during use. Below 158 ± 5 °C, methyl linoleate behaves as a pro-oxidant, whilst above 158 °C, it inhibits alkane autoxidation. This change of mechanism is consistent with the addition of oxygen molecules to doubly allylic carbon centred radicals formed by hydrogen abstraction from methyl linoleate becoming reversible above 158 °C.

The nearshore Antarctic environment is subject to increasing anthropogenic impact, yet the ecological processes influencing some of its most dominant species remain poorly understood. We examined patterns of the distribution and abundance of the Antarctic amphipod Orchomenella franklini in relation to the local environment. Samples of benthic sediment were collected in East Antarctica across several spatial and temporal scales and were analysed for the abundance of O. franklini and various sediment properties. O. franklini was found to reach extremely high densities ( -2 ), yet abundance was strongly heterogeneous on all spatial scales tested. Temporal variation in abundance was also significant and was location-specific, potentially reflecting fluctuations in food supply and variable conditions resulting from ice disturbance. Principal component analysis and generalised additive modelling revealed evidence of a relationship between the distribution of O. franklini and the sediment, which was consistent with its deposit-feeding trophic niche. Generally, the abundance of O. franklini increased with decreasing sediment grain size and increasing trace element concentration. Abundance also peaked at high (though not maximum) total organic carbon content. This is one of the first empirical demonstrations of a correlation between discrete physical sediment traits and the abundance of an infaunal benthic species in the Antarctic, with evidence consolidated from 2 geographic regions. The influence of local conditions on the abundance of O. franklini provides insight on the heterogeneity of Antarctic benthic ecosystems.

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases1, while rare variants in CDK4, BRCA2, BAP1, and the promoter of TERT, have also been linked to the disease2-5. Here we set out to identify novel high-penetrance susceptibility genes in unexplained cases by sequencing 184 melanoma patients from 105 pedigrees recruited in the United Kingdom, the Netherlands, and Australia that were negative for variants in known predisposition genes. We identify families where melanoma co-segregates with loss-of-function variants in the protection of telomeres 1 (POT1) gene, a proportion of members presenting with an early age of onset and multiple primaries. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide-/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding, leading to increased telomere length. Thus, POT1 variants predispose to melanoma formation via a direct effect on telomeres.

Until April 2007 the MAGIC telescope used a 300 MSamples/s FADC system to sample the shaped PMT signals produced by the captured Cherenkov photons of air showers. Different algorithms to reconstruct the signal from the read-out samples (extractors) have been implemented and are described and compared. Criteria based on the obtained charge and time resolution/bias are defined and used to judge the different extractors, by applying them to calibration, cosmic and pedestal signals. The achievable charge and time resolution have been derived as functions of the incident number of photo-electrons., Accepted for publication in NIM A

Purpose To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi. Methods We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system. Results A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point. Conclusions This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel's high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features. Translational Relevance Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses., Comment: Submitted to NIM A

The blazar Markarian 501 (Mrk 501) was observed at energies above 0.10 TeV with the MAGIC telescope from May through July 2005. The high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis. Throughout our observational campaign, the flux from Mrk 501 was found to vary by an order of magnitude. Intra-night flux variability with flux-doubling times down to 2 minutes was observed during the two most active nights, namely June 30 and July 9. These are the fastest flux variations ever observed in Mrk 501. The ~20-minute long flare of July 9 showed an indication of a 4 +/- 1 min time delay between the peaks of F(1.2 TeV), which may indicate a progressive acceleration of electrons in the emitting plasma blob. The flux variability was quantified for several energy ranges, and found to increase with the energy of the gamma-ray photons. The spectra hardened significantly with increasing flux, and during the two most active nights, a spectral peak was clearly detected at 0.43 +/- 0.06 TeV and 0.25 +/- 0.07 TeV, respectively for June 30 and July 9. There is no evidence of such spectral feature for the other nights at energies down to 0.10 TeV, thus suggesting that the spectral peak is correlated with the source luminosity. These observed characteristics could be accommodated in a Synchrotron-Self-Compton (SSC) framework in which the increase in gamma-ray flux is produced by a freshly injected (high energy) electron population.

During its first data cycle, between 2005 and the beginning of 2006, the fast repositioning system of the MAGIC telescope allowed the observation of nine different gamma-ray bursts as possible sources of very high energy gamma-rays. These observations were triggered by alerts from Swift, HETE-2, and INTEGRAL; they started as quickly as possible after the alerts and lasted for several minutes, with an energy threshold varying between 80 and 200 GeV, depending on the zenith angle of the burst. No evidence for gamma signals was found, and upper limits for the flux were derived for all events using the standard analysis chain of MAGIC. For the bursts with measured redshifts, the upper limits are compatible with a power-law extrapolation, when the intrinsic fluxes are evaluated taking into account the attenuation due to the scattering in the metagalactic radiation field.

A hallmark of cancer is genomic instability that is considered to provide the adaptive capacity of cancers to thrive under conditions in which the normal precursors would not survive. Recent genomic analysis has revealed a very high degree of genomic instability in melanomas, although the mechanism by which this instability arises is not known. Here we report that a high proportion (68%) of melanoma cell lines are either partially (40%) or severely (28%) compromised for the G2 phase decatenation checkpoint that normally functions to ensure that the sister chromatids are able to separate correctly during mitosis. The consequence of this loss of checkpoint function is a severely reduced ability to partition the replicated genome in mitosis and thereby increase genomic instability. We also demonstrate that decatenation is dependent on both TopoIIα and β isoforms. The high incidence of decatenation checkpoint defect is likely to be a major contributor to the high level of genomic instability found in melanomas.

Shallow-water benthic communities throughout coastal Antarctica share many spe- cies and are governed by similar physico-oceanographic processes. This suggests community structure and function may be similar among communities despite being geographically sepa- rated by up to 15 degrees of latitude and 18 000 km of coastline. To test this theory, we developed a food web model using stable isotopes (δ 13 C, δ 15 N) for the high-latitude Vestfold Hills shallow- water benthic community and compared it to the isotopic food web model developed for the Wind- mill Islands, located over 1000 km away. For the Vestfold Hills food web, carbon sources were generally well separated by δ 13 C, and lower-order consumers could be grouped according to their feeding guild and main dietary sources as determined by δ 13 C and δ 15 N. Higher-order consumers occupied the full range of δ 13 C ratios and had similar δ 15 N values, although predators were weakly, but significantly, enriched in δ 15 N compared to scavenger/predators and omnivores. When comparing with the Windmill Islands food web, we found similar δ 13 C ratios for several co- occurring carbon sources and consumers, whilst the δ 15 N ratios in consumers from the Vestfold Hills were consistently enriched compared to those from the Windmill Islands by 1 to 2‰. The rel- ative positions of feeding guilds on the δ 13 C and δ 15 N planes were similar for both food webs. These results suggest there is considerable merit in developing a representative food web model for Antarctic shallow-water communities. Such a model would provide a trophic benchmark against which modification in these communities brought about by climate change or other human impacts could be compared.

Oil pollution across Antarctica is low compared with other regions of the world, concentrated at sites of human activity near rare ice-free coastal areas. It occurs from a range of activities including national Antarctic programs, tourism and fishing. Historic sources exist from abandoned infrastructure and stations, vehicle wrecks, waste disposal sites, waste water discharge, and past whaling activities. The oils polluting the Antarctic environment are varied and so are the residual properties and toxicities as a result of differing degrees of weathering and degradation.

Melanoma is a complex multifactorial disease; therefore, a combination of various approaches is necessary to girt all aspects of its biology and identify the many different genes and factors involved in its etiology.Epigenetic regulation of tumor suppressor genes (TSGs) has been shown to play a central role in melanomagenesis. Here, we describe a new pipeline based on an integrative and comparative analysis of several array platform, post-demethylation treatment expression data, methylation array, and constitutive mRNA expression analysis to identify novel TSGs frequently methylated in melanoma.

On polar coasts, seasonal sea-ice duration strongly influences shallow marine environments by affecting environmental conditions, such as light, sedimentation, and physical disturbance. Sea-ice dynamics are changing in response to climate, but there is limited understanding of how this might affect shallow marine environments and benthos. Here we present a unique set of physical and biological data from a single region of Antarctic coast, and use it to gain insights into factors shaping polar benthic communities. At sites encompassing a gradient of sea-ice duration, we measured temporal and spatial variation in light and sedimentation and hard-substrate communities at different depths and substrate orientations. Biological trends were highly correlated with sea-ice duration, and appear to be driven by opposing gradients in light and sedimentation. As sea-ice duration decreased, there was increased light and reduced sedimentation, and concurrent shifts in community structure from invertebrate to algal dominance. Trends were strongest on shallower, horizontal surfaces, which are most exposed to light and sedimentation. Depth and substrate orientation appear to mediate exposure of benthos to these factors, thereby tempering effects of sea-ice and increasing biological heterogeneity. However, while light and sedimentation both varied spatially with sea-ice, their dynamics differed temporally. Light was sensitive to the site-specific date of sea-ice breakout, whereas sedimentation fluctuated at a regional scale coincident with the summer phytoplankton bloom. Sea-ice duration is clearly the overarching force structuring these shallow Antarctic benthic communities, but direct effects are imposed via light and sedimentation, and mediated by habitat characteristics.

We present a comprehensive scientific assessment of the environmental impacts of an Antarctic wastewater ocean outfall, at Davis station in East Antarctica. We assessed the effectiveness of current wastewater treatment and disposal requirements under the Protocol on Environmental Protection to the Antarctic Treaty. Macerated wastewater has been discharged from an outfall at Davis since the failure of the secondary treatment plant in 2005. Water, sediment and wildlife were tested for presence of human enteric bacteria and antibiotic resistance mechanisms. Epibiotic and sediment macrofaunal communities were tested for differences between sites near the outfall and controls. Local fish were examined for evidence of histopathological abnormalities. Sediments, fish and gastropods were tested for uptake of sewage as measured by stable isotopes of N and C. Escherichia coli carrying antibiotic resistance determinants were found in water, sediments and wildlife (the filter feeding bivalve Laternula eliptica). Fish (Trematomus bernacchii) within close proximity to the outfall had significantly more severe and greater occurrences of histopathological abnormalities than at controls, consistent with exposure to sewage. There was significant enrichment of 15N in T. bernacchii and the predatory gastropod Neobuccinum eatoni around the outfall, providing evidence of uptake of sewage. There were significant differences between epibiotic and sediment macrofaunal communities at control and outfall sites (

An investigation has been carried out to characterize and evaluate phenolic compounds of bio-oils produced by the microwave enhanced pyrolysis of spruce woodchips (picea abies) for their potential application in stabilizing biodiesel from autoxidation. Four extracts were isolated from the bio-oil through multi-fractionation steps using a liquid–liquid extraction method: water-soluble, neutral, phenolic and organic acids extracts. The crude bio-oil and the isolated extracts were characterized by GC-MS, GC-FID, total phenols by Folin–Ciocalteu assay, ATR-IR and 13C NMR. The antioxidative effect of the crude bio-oil, its isolated extracts and two significant phenolic components (eugenol and catechol) of the crude bio-oil were also investigated using methyl linoleate as a biodiesel model by means of a high temperature (120 °C) oxidation test. The results show that methyl linoleate induction time increased after blending small amounts (1.4–5.6% w/w) of either the crude bio-oil or the isolated extracts. However, the crude bio-oil showed higher induction times in comparison with its isolated extracts, which was significant because the crude bio-oil contained a lower concentration of phenolic species (23% w/w), especially in comparison to the phenolic concentration in the phenolic extract (49.6% w/w). Furthermore, catechol was found to be very effective and was similar to crude bio-oil in the inhibition of methyl linoleate autoxidation, unlike eugenol, which was less effective at equivalent molar concentrations. Also, the effect of catechol and the crude bio-oil on methyl linoleate induction time was approximately comparable with a commercial antioxidant (butylated hydroxytoluene) when treated at equivalent molar concentration of phenols.

Comprehensive ecological research is still lacking for many of the species that dominate the Antarctic benthos, preventing an adequate understanding of their potential response to environmental change. Here, population dynamics were explored in one of the most ubiquitous nearshore Antarctic benthic amphipods, Orchomenella franklini. Sex, reproductive status and body length were recorded for over 6,000 individuals, sampled from a variety of locations and times at Casey station in East Antarctica. Several life history traits were revealed for O. franklini that exemplify adaptations predicted for a polar environment. These include delayed reproduction, extended brood incubation, low fecundity, longevity and seasonal breeding linked to the summer phytoplankton bloom. There was also preliminary evidence of inter-annual and spatial fluctuations in population structure, potentially reflecting local environmental heterogeneity such as sea-ice duration. The influence of both large scale and local environmental conditions on the ecology of O. franklini provides insight into the vulnerability of this species to environmental change.

Partial discharges may cause damage to electrical insulation of high voltage equipment. They initiate elastic waves in the insulating material, e.g. in the stress cone of an outdoor termination. Localisation of the origin of such elastic waves can help to predict serious damaging processes in the electrical insulation. In order to measure and evaluate the wave propagation effects in typical multilayered elastomeric structures, knowledge of the material properties is required. The propagating velocity and the attenuation of longitudinal waves are important parameters. Values for these quantities found in the literature were not appropriate. Therefore, for cross-linked polyethylene (XLPE) and cured liquid silicone rubber (LSR), the longitudinal wave velocity and the attenuation were evaluated in the temperature interval from -20°C to 50°C and in the frequency range from 200 kHz to 600 kHz using a two-sample ultrasound technique. The loss factor was determined from these measured quantities. Additionally, low frequency Dynamic Mechanical Thermal Analysis (DMTA) was applied to investigate LSR and XLPE in a temperature interval between -100 and 50°C and to check qualitatively the ultrasound data.

High density SNP arrays can be used to identify DNA copy number changes in tumors such as homozygous deletions of tumor suppressor genes and focal amplifications of oncogenes. Illumina Human CNV370 Bead chip arrays were used to assess the genome for unbalanced chromosomal events occurring in 39 cell lines derived from stage III metastatic melanomas. A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39). In addition, a number of focal homozygous deletions potentially targeting novel melanoma tumor suppressor genes were identified. Because of their likely functional significance for melanoma progression, FAS, CH25H, BMPR1A, ACTA2, and TFG were investigated in a larger cohort of melanomas through sequencing. Nonsynonymous mutations were identified in BMPR1A (1 of 43), ACTA2 (3 of 43), and TFG (5 of 103). A number of potentially important mutation events occurred in TFG including the identification of a mini mutation "hotspot" at amino acid residue 380 (P380S and P380L) and the presence of multiple mutations in two melanomas. Mutations in TFG may have important clinical relevance for current therapeutic strategies to treat metastatic melanoma.

Stable isotopes of carbon and nitrogen were used to determine the different carbon pathways and trophic assemblages amongst coastal benthic fauna of the Windmill Islands, East Antarctica. Macroalgae, pelagic POM, sediment POM and sea ice POM had well-separated δ 13 C signatures, which ranged from −36.75‰ for the red alga Phyllophora antarctica , to −10.35‰ for sea ice POM. Consumers were also well separated by δ 13 C, ranging from −21.42‰ for the holothurian Staurocucumis sp. up to −7.47‰ for the urchin Sterechinus neumayeri . Analysis of δ 13 C and δ 15 N revealed distinct groups for suspension feeders, grazer/herbivores and deposit feeders, whilst predators and predator/scavengers showed less grouping. Consumers spanned a δ 15 N range of 8.71‰, equivalent to four trophic levels, although δ 15 N ratios amongst consumers were continuous, rather than grouped into discrete trophic levels. The study has built a trophic model for the Windmill Islands and summarises three main carbon pathways utilised by the benthos: (1) pelagic POM; (2) macroalgae/epiphytic/benthic diatoms and (3) sediment POM/benthic diatoms. The movement of carbon within the coastal benthic community of the Windmill Islands is considered complex, and stable isotopes of carbon and nitrogen were valuable tools in determining specific feeding guilds and in tracing carbon flow, particularly amongst lower-order consumers.