Optimising Selective Sampling for Bootstrapping Named Entity Recognition

Training a statistical named entity recognition system in a new domain requires costly manual annotation of large quantities of in-domain data. Active learning promises to reduce the annotation cost by selecting only highly informative data points. This paper is concerned with a real active learning experiment to bootstrap a named entity recognition system for a new domain of radio astronomical abstracts. We evaluate several committee-based metrics for quantifying the disagreement between classifiers built using multiple views, and demonstrate that the choice of metric can be optimised in simulation experiments with existing annotated data from different domains. A final evaluation shows that we gained substantial savings compared to a randomly sampled baseline. 1

Conserved substitution patterns around nucleosome footprints in eukaryotes and Archaea derive from frequent nucleosome repositioning through evolution.

Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested to influence the evolution of eukaryotic genomes, both by altering the propensity of DNA to mutate and by selection acting to maintain or exclude nucleosomes in particular locations. Contrary to the popular idea that nucleosomes are unique to eukaryotes, histone proteins have also been discovered in some archaeal genomes. Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in many respects, including their assembly into tetramers (rather than octamers) from histone proteins that lack N- and C-terminal tails. Here, we show that despite these fundamental differences the association between nucleosome footprints and sequence evolution is strikingly conserved between humans and the model archaeon Haloferax volcanii. In light of this finding we examine whether selection or mutation can explain concordant substitution patterns in the two kingdoms. Unexpectedly, we find that neither the mutation nor the selection model are sufficient to explain the observed association between nucleosomes and sequence divergence. Instead, we demonstrate that nucleosome-associated substitution patterns are more consistent with a third model where sequence divergence results in frequent repositioning of nucleosomes during evolution. Indeed, we show that nucleosome repositioning is both necessary and largely sufficient to explain the association between current nucleosome positions and biased substitution patterns. This finding highlights the importance of considering the direction of causality between genetic and epigenetic change

Reward Enhances Pain Discrimination in Humans

The notion that reward inhibits pain is a well-supported observation in both humans and animals, allowing suppression of pain reflexes to acquired rewarding stimuli. However, a blanket inhibition of pain by reward would also impair pain discrimination. In contrast, early counterconditioning experiments implied that reward might actually spare pain discrimination. To test this hypothesis, we investigated whether discriminative performance was enhanced or inhibited by reward. We found in adult human volunteers (N = 25) that pain-based discriminative ability is actually enhanced by reward, especially when reward is directly contingent on discriminative performance. Drift-diffusion modeling shows that this relates to an augmentation of the underlying sensory signal strength and is not merely an effect of decision bias. This enhancement of sensory-discriminative pain-information processing suggests that whereas reward can promote reward-acquiring behavior by inhibition of pain in some circumstances, it can also facilitate important discriminative information of the sensory input when necessary

Small Molecule Modulators of Dauer Formation and Longevity in Caenorhabditis Elegans

7-ketocholesterol modulates dauer formation and longevity via DAF-12 Ageing is the inevitable fate of most living organisms, and is the greatest risk factor for many diseases such as diabetes, cancer, cardiovascular disorders and neurodegeneration. Deceleration of ageing delays the onset of such diseases and improves health into old age. On the cellular level, several signaling pathways that integrate the nutrient sensors insulin/IGF-1-like signaling (IIS) and target of rapamycin (TOR) play an important role in the modulation of lifespan. Downstream effectors of these pathways include broad cellular functions such as protein translation, mitochondrial activity, autophagy and protein homeostasis, affecting youthfulness of cells and the whole organism. Some of these lifespan modulators were found to be direct targets of small molecules such as glucose and rapamycin. In this study, we asked how might endogenous small molecule metabolites including components of the diet such as sugars, amino acids and fatty acids modulate lifespan? What signaling pathways are involved? How can they be used to alter the onset of age-related diseases and potentially help to develop drugs or even prevent them? Interestingly, many pathways and signals regulating lifespan in C. elegans were originally discovered for their role in regulating the dauer decision. C. elegans arrest at the stress-resistant long-lived dauer stage in response to harsh environmental conditions such as high temperature, food scarcity, or high population density. In brief, inhibition the IIS pathway, and resulting transcriptional activity of phosphorylated DAF-16/FOXO activates a hormone biosynthetic pathway that converts cholesterol into bile acid like steroids called the dafachronic acids (DA). DAs are endogenous ligands of the steroid receptor DAF-12, a homolog of mammalian LXR/FXR/VDR, and key determinant of dauer formation. Liganded DAF-12 promotes reproductive development and normal life. Conversely, when these pathways are down-regulated, the unliganded DAF-12 represses these programs and promotes dauer formation and long life. To identify novel signaling molecules regulating life span, we performed a screen for small molecule metabolites that modulate dauer formation in the insulin receptor mutant daf-2(e1368) background. daf-2(e1368) displays a temperature sensitive constitutive dauer formation (Daf-c) phenotype that can be enhanced or suppressed. Our premise was that molecules identified as dauer modulators may also be good candidates for modulating lifespan. We supplemented small molecules involved in energy homeostasis and metabolism such as sugars, amino acids, fatty acids and steroids, and measured dauer formation at a semi-permissive temperature as first readout. From such screens we identified sugars (glucose, galactose, trehalose), amino acids (tryptophan, glycine) and a fatty acid (arachidonic acid) that reduce dauer formation, suggesting they could activate reproductive programs. Interestingly, we also identified 7-ketocholesterol (7-KC) as potent synergistic enhancer of daf-2 dauer formation and focused on this molecule as a potential modulator of longevity. Although 7-KC had little effect on wild type dauer formation, it enhanced dauer formation of various Daf-c mutants of the dauer signaling pathways including daf-2/InsR, daf-7/TGFβ, the Niemann Pick Type C1 homologs, as well as several mutants involved in DA production such as daf-36/Rieske oxygenase. Using a biochemical GC-MS approach, we found that 7-KC altered sterol profiles and exhibited an increase in whole body cholesterol but a decrease in 7-dehydrocholesterol, suggesting possible effects on the first step in Δ7-DA synthesis. Moreover, 7-KC induced hypodermal daf-9/CYP27A1 expression, a marker of mild DA depletion in wild type animals. Importantly, 7-KC was found to extend median lifespan of wild type animals by 20%, in a manner independent of DAF-16/FOXO but dependent on DAF-12/FXR, as well as on the hormone biosynthetic enzyme DAF-9/CYP27A1. In vivo mRNA analyses revealed that 7-KC modestly interferes with expression of DAF-12 target genes (mir-84, mir-48 and mir-241). Accordingly, competition assays suggest that 7-KC thwarts DAF-12 transcriptional activity in cell culture. Whole transcriptome analyses (RNAseq) in C. elegans revealed that 7-KC induces changes in gene expression consistent with regulatory effects on DAF-12 as well as the DAF-12 related receptor, NHR-8. The inferred changes in gene expression suggests that 7-KC opposes known DAF-12 target gene expression and in addition potentially drives a different subset of genes. Taken together, we hypothesize that 7-KC might be converted to an alternative DA-like molecule, 7-keto-DA by DAF-9. In this view, 7-keto-DA might be an alternate DAF-12 ligand, mediating the observed phenotypes. 7-KC is found in all living organisms including humans, where it may be involved in the regulation of bile acid and de novo cholesterol synthesis. Moreover 7-KC was shown to be involved in the formation of age related atherosclerotic cardiovascular disease. Our findings might lead to identification of novel direct mammalian 7-KC target genes and might provide a first step to clarify if 7-KC plays a causative role in atherosclerosis

Climate Change Impacts on International Seaports: Knowledge, Perceptions, and Planning Efforts Among Port Administrators

Seaports are located in vulnerable areas to climate change impacts: on coasts susceptible to sea-level rise and storms or at mouths of rivers susceptible to flooding. They serve a vital function within the local, regional, and global economy. Their locations in the heart of sensitive estuarine environments make it an imperative to minimize the impacts of natural hazards. Climate impacts, like a projected SLR of .6m to 2m and doubling of Category 4 and 5 hurricanes by 2100, will result in more extreme events at many seaports. To assess the current state of knowledge on this issue, we surveyed port authorities from around the world about how administrators felt climate change might impact their operations, what sea-level change would create operational problems, and how they planned to adapt to new environmental conditions. The planned rapid expansion of ports reported by the survey respondents indicates that adaptation measures should be considered as ports construct new infrastructure that may still be in use at the end of the century. Respondents agreed that the ports community needs to address this issue and most felt relatively uninformed about potential climate impacts. Although most ports felt that SLR would not be an issue at their port this century, sea-level rise was nevertheless an issue of great concern. Our results suggest opportunities for the scientific community to engage with port practitioners to prepare proactively for climate change impacts on this sector

Evidence for dopaminergic involvement in endogenous modulation of pain relief

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here, we studied pain modulation during a probabilistic relief-seeking task (a ‘wheel of fortune’ gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa enhanced each of these information-specific aspects of relief modulation but no significant effects of the opioidergic manipulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior

A Method to Estimate Climate-Critical Construction Materials Applied to Seaport Protection

Climate adaptation for coastal infrastructure projects raises unique challenges because global-scale environmental changes may require similar projects to be completed in many locations over the same time frame. Existing methods to forecast resource demand and capacity do not consider this phenomenon of a global change affecting many localities and the resulting increased demand for resources. Current methods do not relate to the most up-to-date climate science information, and they are too costly or too imprecise to generate global, regional, and local forecasts of “climate-critical resources” that will be required for infrastructure protection. They either require too much effort to create the many localized designs or are too coarse to consider information sources about local conditions and structure-specific engineering knowledge. We formalized the concept of a “minimum assumption credible design” (MACD) to leverage available local information (topography/bathymetry and existing infrastructure) and the essential engineering knowledge and required construction materials (i.e., a design cross-section template). The aggregation of the resources required for individual local structures then forecasts the resource demand for global adaptation projects. We illustrate the application of the MACD method to estimate the demand for construction materials critical to protect seaports from sea-level-rise-enhanced storm surges. We examined 221 of the world’s 3,300+ seaports to calculate the resource requirements for a coastal storm surge protection structure suited to current upper-bound projections of two meters of sea level rise by 2100. We found that a project of this scale would require approximately 436 million cubic meters of construction materials, including cement, sand, aggregate, steel rebar, and riprap. For cement alone, ∼49 million metric tons would be required. The deployment of the MACD method would make resource forecasts for adaptation projects more transparent and widely accessible and would highlight areas where current engineering knowledge or material, engineering workforce, and equipment capacity fall short of meeting the demands of adaptation projects