The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/1/sim8445_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/2/sim8445.pd

Associative and Spatial Relationships in Thesaurus-based Retrieval

The OASIS (Ontologically Augmented Spatial Information System) project explores terminology systems for thematic and spatial access in digital library applications. A prototype implementation uses data from the Royal Commission on the Ancient and Historical Monuments of Scotland, together with the Getty AAT and TGN thesauri. This paper describes its integrated spatial and thematic schema and discusses novel approaches to the application of thesauri in spatial and thematic semantic distance measures. Semantic distance measures can underpin interactive and automatic query expansion techniques by ranking lists of candidate terms. We first illustrate how hierarchical spatial relationships can be used to provide more flexible retrieval for queries incorporating place names in applications employing online gazetteers and geographical thesauri. We then employ a set of experimental scenarios to investigate key issues affecting use of the associative (RT) thesaurus relationships in semantic distance measures. Previous work has noted the potential of RTs in thesaurus search aids but the problem of increased noise in result sets has been emphasised. Specialising RTs allows the possibility of dynamically linking RT type to query context. Results presented in this paper demonstrate the potential for filtering on the context of the RT link and on subtypes of RT relationships

Young and Intermediate-age Distance Indicators

Distance measurements beyond geometrical and semi-geometrical methods, rely mainly on standard candles. As the name suggests, these objects have known luminosities by virtue of their intrinsic proprieties and play a major role in our understanding of modern cosmology. The main caveats associated with standard candles are their absolute calibration, contamination of the sample from other sources and systematic uncertainties. The absolute calibration mainly depends on their chemical composition and age. To understand the impact of these effects on the distance scale, it is essential to develop methods based on different sample of standard candles. Here we review the fundamental properties of young and intermediate-age distance indicators such as Cepheids, Mira variables and Red Clump stars and the recent developments in their application as distance indicators.Comment: Review article, 63 pages (28 figures), Accepted for publication in Space Science Reviews (Chapter 3 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Shedding light on the ‘dark side’ of phylogenetic comparative methods

ORCID: 0000-0003-4919-8655© 2016 The Authors. Methods in Ecology and Evolution published by John Wiley & Sons Ltd on behalf of British Ecological Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The attached file is the published version of the article

Dysregulation of the Norepinephrine Transporter Sustains Cortical Hypodopaminergia and Schizophrenia-Like Behaviors in Neuronal Rictor Null Mice

A novel animal model highlights the link between Akt dysfunction, reduced cortical dopamine function, norepinephrine transporters, and schizophrenia-like behaviors

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity

<p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.</p> <p>Methods</p> <p>A549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.</p> <p>Results</p> <p>Pretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.</p> <p>Conclusions</p> <p>Psammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.</p

Environmental Controls and Anthropogenic Impacts on Deep-Sea Sponge Grounds in the Faroe-Shetland Channel, NE Atlantic: the Importance of Considering Spatial Scale to Distinguish Drivers of Change

Determining the scale of anthropogenic impacts is critical in order to understand ecosystem effects of human activities, within the context of changes caused by natural environmental variability. We applied spatial eigenfunction analysis to disentangle effects of anthropogenic drivers from environmental factors on species assembly in the Faroe-Shetland Channel (FSC), in the northeast Atlantic. We found that the species assembly considered here was structured at both small and large spatial scales. Specifically, substrate types, distance to oil wells and pipelines, the presence of objects and demersal fishing (both static and mobile) appeared significant in explaining large spatial scale species assembly structures. Conversely, temperature and variance in temperature shaped the species community across smaller spatial scales. Mobile scavenger species were found in areas impacted by demersal fishing. Oil and gas structures seemed to provide a habitat for a range of species including the commercially important fishes Molva sp. and Sebastes sp. These results demonstrate how the benthic ecosystem in the FSC has been shaped by multiple human activities, at both small and large spatial scales. Only by sampling datasets covering several sites, like in this study, can the effects of anthropogenic activities be separated from natural environmental controls

Magnetic Resonance Imaging in Huntington's Disease.

Magnetic resonance imaging (MRI) is a noninvasive technique used routinely to image the body in both clinical and research settings. Through the manipulation of radio waves and static field gradients, MRI uses the principle of nuclear magnetic resonance to produce images with high spatial resolution, appropriate for the investigation of brain structure and function