The GNAT library for local and remote gene mention normalization

Summary: Identifying mentions of named entities, such as genes or diseases, and normalizing them to database identifiers have become an important step in many text and data mining pipelines. Despite this need, very few entity normalization systems are publicly available as source code or web services for biomedical text mining. Here we present the Gnat Java library for text retrieval, named entity recognition, and normalization of gene and protein mentions in biomedical text. The library can be used as a component to be integrated with other text-mining systems, as a framework to add user-specific extensions, and as an efficient stand-alone application for the identification of gene and protein names for data analysis. On the BioCreative III test data, the current version of Gnat achieves a Tap-20 score of 0.1987

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances

This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches

Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates.

The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone resistance in Campylobacter and track resistance trends in human clinical isolates in relation to use of these agents in food animals. Susceptibility data suggest that erythromycin and other macrolides should remain the drugs of choice in most regions, with systematic surveillance and control measures maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions

Myosin II regulates the shape of three-dimensional intestinal epithelial cysts.

The development of luminal organs begins with the formation of spherical cysts composed of a single layer of epithelial cells. Using a model three-dimensional cell culture, this study examines the role of a cytoskeletal motor, myosin II, in cyst formation. Caco-2 and SK-CO15 intestinal epithelial cells were embedded into Matrigel, and myosin II was inhibited by blebbistatin or siRNA-mediated knockdown. Whereas control cells formed spherical cysts with a smooth surface, inhibition of myosin II induced the outgrowth of F-actin-rich surface protrusions. The development of these protrusions was abrogated after inhibition of F-actin polymerization or of phospholipase C (PLC) activity, as well as after overexpression of a dominant-negative ADF/cofilin. Surface protrusions were enriched in microtubules and their formation was prevented by microtubule depolymerization. Myosin II inhibition caused a loss of peripheral F-actin bundles and a submembranous extension of cortical microtubules. Our findings suggest that inhibition of myosin II eliminates the cortical F-actin barrier, allowing microtubules to reach and activate PLC at the plasma membrane. PLC-dependent stimulation of ADF/cofilin creates actin-filament barbed ends and promotes the outgrowth of F-actin-rich protrusions. We conclude that myosin II regulates the spherical shape of epithelial cysts by controlling actin polymerization at the cyst surface

Widespread deuteration across the IRDC G035.39-00.33

© 2016 The Authors. Infrared Dark Clouds (IRDCs) are cold, dense regions that are usually found within Giant Molecular Clouds. Ongoing star formation within IRDCs is typically still deeply embedded within the surrounding molecular gas. Characterizing the properties of relatively quiescent IRDCs may therefore help us to understand the earliest phases of the star formation process. Studies of local molecular clouds have revealed that deuterated species are enhanced in the earliest phases of star formation. In this paper, we test this towards IRDC G035.39-00.33. We present an 80 arcsec by 140 arcsec map of the J = 2 → 1 transition of N2D+, obtained with the Institut de Radioastronomie Millimétrique 30 m telescope telescope. We find that N2D+ is widespread throughout G035.39-00.33. Complementary observations of N2H+ (1 - 0) are used to estimate the deuterium fraction, DN2H+ frac ≡ N(N2D+)/N(N2H+). We report a mean DN2H+ frac = 0.04 ± 0.01, with a maximum of DN2H+ frac = 0.09 ± 0.02. The mean deuterium fraction is ~3 orders of magnitude greater than the interstellar [D]/[H] ratio. High angular resolution observations are required to exclude beam dilution effects of compact deuterated cores. Using chemical modelling, we find that the average observed values of DN2H+ frac are in agreement with an equilibrium deuterium fraction, given the general properties of the cloud. This implies that the IRDC is at least ~3 Myr old, which is ~8 times longer than the mean free-fall time of the observed deuterated region

Peak Troponin I Levels Are Associated with Functional Outcome in Intracerebral Hemorrhage

Background: Troponin I is a widely used and reliable marker of myocardial damage and its levels are routinely measured in acute stroke care. So far, the influence of troponin I elevations during hospital stay on functional outcome in patients with atraumatic intracerebral hemorrhage (ICH) is unknown. Methods: Observational single-center study including conservatively treated ICH patients over a 9-year period. Patients were categorized according to peak troponin I level during hospital stay (≤0.040, 0.041–0.500, > 0.500 ng/mL) and compared regarding baseline and hematoma characteristics. Multivariable analyses were performed to investigate independent associations of troponin levels during hospital stay with functional outcome – assessed using the modified Rankin Scale (mRS; favorable 0–3/unfavorable 4–6) – and mortality after 3 and 12 months. To account for possible confounding propensity score (PS)-matching (1: 1; caliper 0.1) was performed accounting for imbalances in baseline characteristics to investigate the impact of troponin I values on outcome. Results: Troponin elevations (> 0.040 ng/mL) during hospital stay were observed in 308 out of 745 (41.3%) patients and associated with poorer status on admission (Glasgow Coma Scale/National Institute of Health Stroke Scale). Multivariable analysis revealed troponin I levels during hospital stay to be independently associated with unfavorable outcome after 12 months (risk ratio [95% CI]: 1.030 [1.009–1.051] per increment of 1.0 ng/mL; p = 0.005), but not with mortality. After PS-matching, patients with troponin I elevation (≥0.040 ng/mL) versus those without had a significant higher rate of ­unfavorable outcome after 3 and 12 months (mRS 4–6 at 3 months: < 0.04 ng/mL: 159/265 [60.0%] versus ≥0.04 ng/mL: 199/266 [74.8%]; p < 0.001; at 12 months: < 0.04 ng/mL: 141/248 [56.9%] versus ≥0.04 ng/mL: 179/251 [71.3%]; p = 0.001). Conclusions: Troponin I elevations during hospital stay occur frequently in ICH patients and are independently associated with functional outcome after 3 and 12 months but not with mortality

Reduced basis isogeometric mortar approximations for eigenvalue problems in vibroacoustics

We simulate the vibration of a violin bridge in a multi-query context using reduced basis techniques. The mathematical model is based on an eigenvalue problem for the orthotropic linear elasticity equation. In addition to the nine material parameters, a geometrical thickness parameter is considered. This parameter enters as a 10th material parameter into the system by a mapping onto a parameter independent reference domain. The detailed simulation is carried out by isogeometric mortar methods. Weakly coupled patch-wise tensorial structured isogeometric elements are of special interest for complex geometries with piecewise smooth but curvilinear boundaries. To obtain locality in the detailed system, we use the saddle point approach and do not apply static condensation techniques. However within the reduced basis context, it is natural to eliminate the Lagrange multiplier and formulate a reduced eigenvalue problem for a symmetric positive definite matrix. The selection of the snapshots is controlled by a multi-query greedy strategy taking into account an error indicator allowing for multiple eigenvalues

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

Background The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Methods Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Results Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s−1 (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. Conclusions In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve bloc

MOA-2010-BLG-477Lb: constraining the mass of a microlensing planet from microlensing parallax, orbital motion and detection of blended light

Microlensing detections of cool planets are important for the construction of an unbiased sample to estimate the frequency of planets beyond the snow line, which is where giant planets are thought to form according to the core accretion theory of planet formation. In this paper, we report the discovery of a giant planet detected from the analysis of the light curve of a high-magnification microlensing event MOA-2010-BLG-477. The measured planet-star mass ratio is $q=(2.181\pm0.004)\times 10^{-3}$ and the projected separation is $s=1.1228\pm0.0006$ in units of the Einstein radius. The angular Einstein radius is unusually large $\theta_{\rm E}=1.38\pm 0.11$ mas. Combining this measurement with constraints on the "microlens parallax" and the lens flux, we can only limit the host mass to the range $0.13<M/M_\odot<1.0$. In this particular case, the strong degeneracy between microlensing parallax and planet orbital motion prevents us from measuring more accurate host and planet masses. However, we find that adding Bayesian priors from two effects (Galactic model and Keplerian orbit) each independently favors the upper end of this mass range, yielding star and planet masses of $M_*=0.67^{+0.33}_{-0.13}\ M_\odot$ and $m_p=1.5^{+0.8}_{-0.3}\ M_{\rm JUP}$ at a distance of $D=2.3\pm0.6$ kpc, and with a semi-major axis of $a=2^{+3}_{-1}$ AU. Finally, we show that the lens mass can be determined from future high-resolution near-IR adaptive optics observations independently from two effects, photometric and astrometric.Comment: 3 Tables, 12 Figures, accepted in Ap