Alginate hydrogel has a negative impact on in vitro collagen 1 deposition by fibroblasts

Hydrogels have been widely investigated as 3D culture substrates because of their reported structural similarity to the extracellular matrix (ECM). Limited ECM deposition, however, occurs within these materials, so the resulting “tissues” bear little resemblance to those found in the body. Here matrix deposition by fibroblasts encapsulated within a calcium alginate (Ca-alg) hydrogel was investigated. Although the cells transcribed mRNA for coll Iα over a period of 3 weeks, very little collagen protein deposition was observed within the gel by histology or immunohistochemistry (IHC). Although molecular diffusion demonstrated charge dependency, this did not prevent the flux of both positively and negative charged amino acids through the gel, suggesting that the absence of ECM could not be attributed to substrate limitation. The flux of protein, however, was charge-dependent as proteins with a net negative charge passed quickly through the Ca-alg into the medium. The minimal collagen deposition within the Ca-alg was attributed to a combination of rapid movement of negatively charged procollagen through the gel and steric hindrance of fibril formation

Observing the dynamics of super-massive black hole binaries with Pulsar Timing Arrays

Pulsar Timing Arrays are a prime tool to study unexplored astrophysical regimes with gravitational waves. Here we show that the detection of gravitational radiation from individually resolvable super-massive black hole binary systems can yield direct information about the masses and spins of the black holes, provided that the gravitational-wave induced timing fluctuations both at the pulsar and at the Earth are detected. This in turn provides a map of the non-linear dynamics of the gravitational field and a new avenue to tackle open problems in astrophysics connected to the formation and evolution of super-massive black holes. We discuss the potential, the challenges and the limitations of these observations.Comment: 5 pages, 1 figur

Datasets for generic relation extraction

A vast amount of usable electronic data is in the form of unstructured text. The relation extraction task aims to identify useful information in text (e.g. PersonW works for OrganisationX, GeneY encodes ProteinZ) and recode it in a format such as a relational database or RDF triplestore that can be more effectively used for querying and automated reasoning. A number of resources have been developed for training and evaluating automatic systems for relation extraction in different domains. However, comparative evaluation is impeded by the fact that these corpora use different markup formats and notions of what constitutes a relation. We describe the preparation of corpora for comparative evaluation of relation extraction across domains based on the publicly available ACE 2004, ACE 2005 and BioInfer data sets. We present a common document type using token standoff and including detailed linguistic markup, while maintaining all information in the original annotation. The subsequent reannotation process normalises the two data sets so that they comply with a notion of relation that is intuitive, simple and informed by the semantic web. For the ACE data, we describe an automatic process that automatically converts many relations involving nested, nominal entity mentions to relations involving non-nested, named or pronominal entity mentions. For example, the first entity is mapped from 'one' to 'Amidu Berry' in the membership relation described in 'Amidu Berry, one half of PBS'. Moreover, we describe a comparably reannotated version of the BioInfer corpus that flattens nested relations, maps part-whole to part-part relations and maps n-ary to binary relations. Finally, we summarise experiments that compare approaches to generic relation extraction, a knowledge discovery task that uses minimally supervised techniques to achieve maximally portable extractors. These experiments illustrate the utility of the corpora.39 page(s

Constant-time solution to the Global Optimization Problem using Bruschweiler's ensemble search algorithm

A constant-time solution of the continuous Global Optimization Problem (GOP) is obtained by using an ensemble algorithm. We show that under certain assumptions, the solution can be guaranteed by mapping the GOP onto a discrete unsorted search problem, whereupon Bruschweiler's ensemble search algorithm is applied. For adequate sensitivities of the measurement technique, the query complexity of the ensemble search algorithm depends linearly on the size of the function's domain. Advantages and limitations of an eventual NMR implementation are discussed.Comment: 14 pages, 0 figure

Interpretation and the Constraints on International Courts

This paper argues that methodologies of interpretation do not do what they promise – they do not constrain interpretation by providing neutral steps that one can follow in finding out a meaning of a text – but nevertheless do their constraining work by being part of what can be described as the legal practice

An Adaptive Framework for Selecting Environmental Monitoring Protocols to Support Ocean Renewable Energy Development

Offshore renewable energy developments (OREDs) are projected to become common in the United States over the next two decades. There are both a need and an opportunity to guide efforts to identify and track impacts to the marine ecosystem resulting from these installations. A monitoring framework and standardized protocols that can be applied to multiple types of ORED would streamline scientific study, management, and permitting at these sites. We propose an adaptive and reactive framework based on indicators of the likely changes to the marine ecosystem due to ORED. We developed decision trees to identify suites of impacts at two scales (demonstration and commercial) depending on energy (wind, tidal, and wave), structure (e.g., turbine), and foundation type (e.g., monopile). Impacts were categorized by ecosystem component (benthic habitat and resources, fish and fisheries, avian species, marine mammals, and sea turtles) and monitoring objectives were developed for each. We present a case study at a commercial-scale wind farm and develop a monitoring plan for this development that addresses both local and national environmental concerns. In addition, framework has provided a starting point for identifying global research needs and objectives for understanding of the potential effects of ORED on the marine environment

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some C. jejuni strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized. We combined pangenome-wide association studies and phenotypic assays to compare C. jejuni isolates from patients who developed PI-IBS with those who did not. We show that variation in bacterial stress response (Cj0145_phoX), adhesion protein (Cj0628_CapA), and core biosynthetic pathway genes (biotin: Cj0308_bioD; purine: Cj0514_purQ; isoprenoid: Cj0894c_ispH) were associated with PI-IBS development. In vitro assays demonstrated greater adhesion, invasion, IL-8 and TNFα secretion on colonocytes with PI-IBS compared to PI-no-IBS strains. A risk-score for PI-IBS development was generated using 22 genomic markers, four of which were from Cj1631c, a putative heme oxidase gene linked to virulence. Our finding that specific Campylobacter genotypes confer greater in vitro virulence and increased risk of PI-IBS has potential to improve understanding of the complex host-pathogen interactions underlying this condition

Fire in Australian savannas: From leaf to landscape

© 2014 The Authors. Global Change Biology Published by John Wiley & Sons Ltd. Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of Australia (almost 1.9 million km2) and provide significant ecosystem services through carbon and water cycles and the maintenance of biodiversity. The current structure, composition and distribution of Australian savannas have coevolved with fire, yet remain driven by the dynamic constraints of their bioclimatic niche. Fire in Australian savannas influences both the biophysical and biogeochemical processes at multiple scales from leaf to landscape. Here, we present the latest emission estimates from Australian savanna biomass burning and their contribution to global greenhouse gas budgets. We then review our understanding of the impacts of fire on ecosystem function and local surface water and heat balances, which in turn influence regional climate. We show how savanna fires are coupled to the global climate through the carbon cycle and fire regimes. We present new research that climate change is likely to alter the structure and function of savannas through shifts in moisture availability and increases in atmospheric carbon dioxide, in turn altering fire regimes with further feedbacks to climate. We explore opportunities to reduce net greenhouse gas emissions from savanna ecosystems through changes in savanna fire management