NOBLE - Flexible concept recognition for large-scale biomedical natural language processing

Background: Natural language processing (NLP) applications are increasingly important in biomedical data analysis, knowledge engineering, and decision support. Concept recognition is an important component task for NLP pipelines, and can be either general-purpose or domain-specific. We describe a novel, flexible, and general-purpose concept recognition component for NLP pipelines, and compare its speed and accuracy against five commonly used alternatives on both a biological and clinical corpus. NOBLE Coder implements a general algorithm for matching terms to concepts from an arbitrary vocabulary set. The system's matching options can be configured individually or in combination to yield specific system behavior for a variety of NLP tasks. The software is open source, freely available, and easily integrated into UIMA or GATE. We benchmarked speed and accuracy of the system against the CRAFT and ShARe corpora as reference standards and compared it to MMTx, MGrep, Concept Mapper, cTAKES Dictionary Lookup Annotator, and cTAKES Fast Dictionary Lookup Annotator. Results: We describe key advantages of the NOBLE Coder system and associated tools, including its greedy algorithm, configurable matching strategies, and multiple terminology input formats. These features provide unique functionality when compared with existing alternatives, including state-of-the-art systems. On two benchmarking tasks, NOBLE's performance exceeded commonly used alternatives, performing almost as well as the most advanced systems. Error analysis revealed differences in error profiles among systems. Conclusion: NOBLE Coder is comparable to other widely used concept recognition systems in terms of accuracy and speed. Advantages of NOBLE Coder include its interactive terminology builder tool, ease of configuration, and adaptability to various domains and tasks. NOBLE provides a term-to-concept matching system suitable for general concept recognition in biomedical NLP pipelines

Ultra-fast early Miocene exhumation of Cavalli Seamount, Northland Plateau, Southwest Pacific Ocean

We present new photographic, petrological, geochronological, and isotopic data for gneissic and granitic rocks obtained from six sample stations on Cavalli Seamount during two cruises in 2002. These data lead to revision of earlier conclusions based on two dredges of schist in 1999. Based on c. 100 Ma ages of zircon cores, and whole rock petrochemistry and tracer isotopes, we interpret the protoliths of paragneisses and orthogneisses to probably have been sedimentary and plutonic correlatives of the Late Cretaceous Houhora Complex. U‐Pb dating of low Th/U zircon rims confirms an earliest Miocene high‐grade metamorphic episode. A cooling history based on Ar‐Ar K‐feldspar dating indicates ultra‐rapid cooling (c. 2000°C/m.y.) and vertical exhumation (c. 100 mm/yr) of the rocks at 19.9 Ma. Our preferred tectonic model relates the amphibolite facies metamorphism to Northland Allochthon emplacement and the rapid exhumation to dextral transtension along the Vening Meinesz Fracture Zone system and/or a rapidly retreating Pacific trench

The association between green space and cause-specific mortality in urban New Zealand: an ecological analysis of green space utility

<b>Background:</b> There is mounting international evidence that exposure to green environments is associated with health benefits, including lower mortality rates. Consequently, it has been suggested that the uneven distribution of such environments may contribute to health inequalities. Possible causative mechanisms behind the green space and health relationship include the provision of physical activity opportunities, facilitation of social contact and the restorative effects of nature. In the New Zealand context we investigated whether there was a socioeconomic gradient in green space exposure and whether green space exposure was associated with cause-specific mortality (cardiovascular disease and lung cancer). We subsequently asked what is the mechanism(s) by which green space availability may influence mortality outcomes, by contrasting health associations for different types of green space. <b>Methods:</b> This was an observational study on a population of 1,546,405 living in 1009 small urban areas in New Zealand. A neighbourhood-level classification was developed to distinguish between usable (i.e., visitable) and non-usable green space (i.e., visible but not visitable) in the urban areas. Negative binomial regression models were fitted to examine the association between quartiles of area-level green space availability and risk of mortality from cardiovascular disease (n = 9,484; 1996 - 2005) and from lung cancer (n = 2,603; 1996 - 2005), after control for age, sex, socio-economic deprivation, smoking, air pollution and population density. <b>Results:</b> Deprived neighbourhoods were relatively disadvantaged in total green space availability (11% less total green space for a one standard deviation increase in NZDep2001 deprivation score, p < 0.001), but had marginally more usable green space (2% more for a one standard deviation increase in deprivation score, p = 0.002). No significant associations between usable or total green space and mortality were observed after adjustment for confounders. <b>Conclusion</b> Contrary to expectations we found no evidence that green space influenced cardiovascular disease mortality in New Zealand, suggesting that green space and health relationships may vary according to national, societal or environmental context. Hence we were unable to infer the mechanism in the relationship. Our inability to adjust for individual-level factors with a significant influence on cardiovascular disease and lung cancer mortality risk (e.g., diet and alcohol consumption) will have limited the ability of the analyses to detect green space effects, if present. Additionally, green space variation may have lesser relevance for health in New Zealand because green space is generally more abundant and there is less social and spatial variation in its availability than found in other contexts

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

Quantum-inspired interferometry with chirped laser pulses

We introduce and implement an interferometric technique based on chirped femtosecond laser pulses and nonlinear optics. The interference manifests as a high-visibility (> 85%) phase-insensitive dip in the intensity of an optical beam when the two interferometer arms are equal to within the coherence length of the light. This signature is unique in classical interferometry, but is a direct analogue to Hong-Ou-Mandel quantum interference. Our technique exhibits all the metrological advantages of the quantum interferometer, but with signals at least 10^7 times greater. In particular we demonstrate enhanced resolution, robustness against loss, and automatic dispersion cancellation. Our interferometer offers significant advantages over previous technologies, both quantum and classical, in precision time delay measurements and biomedical imaging.Comment: 6 pages, 4 figure

Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer

Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen

Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.Work supported by a PRAT fellowship to M.S.W., an NICHD intramural award to C.J.M., NIDCD intramural research program funding to R.S.P., an NIMH intramural award to H.A.C., NIH grants (PAR-02-059, NS 039156) to P.F.W., and an NIH grant (EY022730) to M.T.

Sexual identity, attraction and behaviour in Britain: The implications of using different dimensions of sexual orientation to estimate the size of sexual minority populations and inform public health interventions.

BACKGROUND: Sexual orientation encompasses three dimensions: sexual identity, attraction and behaviour. There is increasing demand for data on sexual orientation to meet equality legislation, monitor potential inequalities and address public health needs. We present estimates of all three dimensions and their overlap in British men and women, and consider the implications for health services, research and the development and evaluation of public health interventions. METHODS: Analyses of data from Britain's third National Survey of Sexual Attitudes and Lifestyles, a probability sample survey (15,162 people aged 16-74 years) undertaken in 2010-2012. FINDINGS: A lesbian, gay or bisexual (LGB) identity was reported by 2·5% of men and 2·4% of women, whilst 6·5% of men and 11·5% of women reported any same-sex attraction and 5·5% of men and 6·1% of women reported ever experience of same-sex sex. This equates to approximately 547,000 men and 546,000 women aged 16-74 in Britain self-identifying as LGB and 1,204,000 men and 1,389,000 women ever having experience of same-sex sex. Of those reporting same-sex sex in the past 5 years, 28% of men and 45% of women identified as heterosexual. INTERPRETATION: There is large variation in the size of sexual minority populations depending on the dimension applied, with implications for the design of epidemiological studies, targeting and monitoring of public health interventions and estimating population-based denominators. There is also substantial diversity on an individual level between identity, behaviour and attraction, adding to the complexity of delivering appropriate services and interventions

Fundamental Strings, Holography, and Nonlinear Superconformal Algebras

We discuss aspects of holography in the AdS_3 \times S^p near string geometry of a collection of straight fundamental heterotic strings. We use anomalies and symmetries to determine general features of the dual CFT. The symmetries suggest the appearance of nonlinear superconformal algebras, and we show how these arise in the framework of holographic renormalization methods. The nonlinear algebras imply intricate formulas for the central charge, and we show that in the bulk these correspond to an infinite series of quantum gravity corrections. We also makes some comments on the worldsheet sigma-model for strings on AdS_3\times S^2, which is the holographic dual geometry of parallel heterotic strings in five dimensions.Comment: 25 page

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss