Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

The Preliminary Evaluation of Liquid Lubricants for Space Applications by Vacuum Tribometry

Four different vacuum tribometers for the evaluation of liquid lubricants for space applications are described. These range from simple ball-on-flat sliders with maximum in-situ control and surface characterization to an instrument bearing apparatus having no in-situ characterization. Thus, the former provides an abundance of surface chemical information but is not particularly simulative of most triboelements. On the other hand, the instrument bearing apparatus is completely simulative, but only allows post-mortem surface chemical information. Two other devices, a four-ball apparatus and a ball-on-plate tribometer, provide varying degrees of surface chemical information and tribo-simulation. Examples of data from each device are presented

The role of Tay indigenous knowledge in climate change adaptation in the Northern Mountainous Region of Vietnam

459-472Through generations of observation and experimentation, the Tay people of Bac Kan Province in the Northern Mountainous Region of Vietnam have developed complex farming systems, cultural practices and an indigenous knowledge base well-suited to their environments. Drawing on data collected through surveys, interviews and focus group discussions, this article first documents some of this knowledge and its role in supporting agricultural production. However, this research also uncovered that contemporary climate change is occurring at rates faster than that knowledge base can meaningfully adjust and adapt. Agricultural productivity was found to be greatly reduced, with men seeking off-farm employment to supplement the loss in income. Agrochemical use has soared and resulted in declines in the health of the local population. Village gender dynamics have also shifted and women have taken on the extra burden of farming. This paper posits that if indigenous knowledge was better integrated into adaptation planning and policies, its conservation and application would enhance resiliency to climate change in indigenous communities and beyond. Simultaneously, it also adds that as the nature, speed and severity of climate change in many marginal areas occur at rates faster than indigenous knowledge can adapt, blended forms of knowledge may offer practical solutions

The role of Tay indigenous knowledge in climate change adaptation in the Northern Mountainous Region of Vietnam

Through generations of observation and experimentation, the Tay people of Bac Kan Province in the Northern Mountainous Region of Vietnam have developed complex farming systems, cultural practices and an indigenous knowledge base well-suited to their environments. Drawing on data collected through surveys, interviews and focus group discussions, this article first documents some of this knowledge and its role in supporting agricultural production. However, this research also uncovered that contemporary climate change is occurring at rates faster than that knowledge base can meaningfully adjust and adapt. Agricultural productivity was found to be greatly reduced, with men seeking off-farm employment to supplement the loss in income. Agrochemical use has soared and resulted in declines in the health of the local population. Village gender dynamics have also shifted and women have taken on the extra burden of farming. This paper posits that if indigenous knowledge was better integrated into adaptation planning and policies, its conservation and application would enhance resiliency to climate change in indigenous communities and beyond. Simultaneously, it also adds that as the nature, speed and severity of climate change in many marginal areas occur at rates faster than indigenous knowledge can adapt, blended forms of knowledge may offer practical solutions

Evaluating the effectiveness of land use management as a natural flood management intervention in reducing the impact of flooding for an upland catchment

Natural flood management (NFM) is a method for reducing flooding by using a catchment-based approach to managing flood risk. Understanding and quantifying the impact of implementing NFM at the catchment scale remains ambiguous with a clear need for robust empirical evidence. A combination of fieldwork, laboratory analysis and modelling was applied to quantify the impacts of land use management changes on catchment flood hazard. Soil hydraulic conductivity was measured under varying land management regimes and used to parameterize a physically based spatially distributed hydrological model (SD-TOPMODEL). A suite of stakeholder informed land management scenarios was modelled, permitting the quantification of the impact of NFM interventions on the timing and the intensity of the peak discharge at the catchment outlet. The findings support the implementation of NFM interventions as a means of reducing flood hazard within a rural upland catchment. Improved soil infiltration provided the greatest reduction in the intensity and delayed timing of the flood peak for a 10-year occurrence storm event (7% reduction in peak runoff and 8% increase in lag time) with similar reductions observed for a 100-year storm event. Catchment wide woodland planting reduced peak flow by 11% during the 100-year event but was not effective during the 10-year event. Riparian buffer strips provided consistent reductions in peak flow and in the timing of the peak across both storm events with no significant differences relating to vegetation age. Critically, we observed that the effect of implementing multiple NFM interventions was not additive and that efficiencies can be made in using this modelling approach to prioritize the most effective outcomes

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

BioInfer: a corpus for information extraction in the biomedical domain

BACKGROUND: Lately, there has been a great interest in the application of information extraction methods to the biomedical domain, in particular, to the extraction of relationships of genes, proteins, and RNA from scientific publications. The development and evaluation of such methods requires annotated domain corpora. RESULTS: We present BioInfer (Bio Information Extraction Resource), a new public resource providing an annotated corpus of biomedical English. We describe an annotation scheme capturing named entities and their relationships along with a dependency analysis of sentence syntax. We further present ontologies defining the types of entities and relationships annotated in the corpus. Currently, the corpus contains 1100 sentences from abstracts of biomedical research articles annotated for relationships, named entities, as well as syntactic dependencies. Supporting software is provided with the corpus. The corpus is unique in the domain in combining these annotation types for a single set of sentences, and in the level of detail of the relationship annotation. CONCLUSION: We introduce a corpus targeted at protein, gene, and RNA relationships which serves as a resource for the development of information extraction systems and their components such as parsers and domain analyzers. The corpus will be maintained and further developed with a current version being available at

Microstructured catalytic hollow fiber reactor for methane steam reforming

Microstructured alumina hollow fibers, which contain a plurality of radial microchannels with significant openings on the inner surface, have been fabricated in this study and used to develop an efficient catalytic hollow fiber reactor. Apart from low mass-transfer resistance, a unique structure of this type facilitates the incorporation of Ni-based catalysts, which can be with or without the aged secondary support, SBA-15. In contrast to a fixed bed reactor, the catalytic hollow fiber reactor shows similar methane conversion, with a gas hourly space velocity that is approximately 6.5 times higher, a significantly greater CO2 selectivity, and better productivity rates. These results demonstrate the advantages of dispersing the catalyst inside the microstructured hollow fiber as well as the potential to reduce the required quantity of catalyst

‘Preparing Ourselves to Become an International Organization’: Thailand Tobacco Monopoly’s Regional and Global Strategies

The Thailand Tobacco Monopoly (TTM) controlled the country\u27s tobacco industry from its formation in the 1940s, until the government dropped restrictions on imported cigarettes in the late 1980s in response to pressure from the United States. The TTM has since competed with transnational tobacco companies (TTCs) in a semi-monopoly market in which TTCs have steadily increased their market share. Coupled with a decline in national smoking prevalence, the result of Thailand\u27s stringent tobacco control agenda, the TTM now accounts for a diminishing share of a contracting market. In response, the monopoly has looked to regional trade liberalisation, and proximity to markets with some of the world\u27s highest smoking rates to expand its operations. Expansion strategies have gone largely unrealised however, and the TTM effectively remains a domestic operation. Using TTM publications, market and trade reports, industry publications, tobacco industry documents and other resources, this paper analyses TTM expansion strategies, and the limited extent to which they have been achieved. This inability to expand its operations has left the monopoly potentially vulnerable to global strategies of its transnational competitors. This article is part of the special issue \u27The Emergence of Asian Tobacco Companies: Implications for Global Health Governance\u27