bluuebunny/crossref_metadata_2025_split huggingface dataset:
Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N‐terminal trimethylation
Authors: Shields Kaitlyn M. , Tooley John G. , Petkowski Janusz J. , Wilkey Daniel W. , Garbett Nichola C. , Merchant Michael L. , Cheng Alan , Schaner Tooley Christine E. 
Published: May 2017

AbstractA subset of B‐cell lymphoma patients have dominant mutations in the histone H3 lysine 27 (H3K27) methyltransferase EZH2, which change it from a monomethylase to a trimethylase. These mutations occur in aromatic resides surrounding the active site and increase growth and alter transcription. We study the N‐terminal trimethylase NRMT1 and the N‐terminal monomethylase NRMT2. They are 50% identical, but differ in key aromatic residues in their active site. Given how these residues affect EZH2 activity, we tested whether they are responsible for the distinct catalytic activities of NRMT1/2. Additionally, NRMT1 acts as a tumor suppressor in breast cancer cells. Its loss promotes oncogenic phenotypes but sensitizes cells to DNA damage. Mutations of NRMT1 naturally occur in human cancers, and we tested a select group for altered activity. While directed mutation of the aromatic residues had minimal catalytic effect, NRMT1 mutants N209I (endometrial cancer) and P211S (lung cancer) displayed decreased trimethylase and increased monomethylase/dimethylase activity. Both mutations are located in the peptide‐binding channel and indicate a second structural region impacting enzyme specificity. The NRMT1 mutants demonstrated a slower rate of trimethylation and a requirement for higher substrate concentration. Expression of the mutants in wild type NRMT backgrounds showed no change in N‐terminal methylation levels or growth rates, demonstrating they are not acting as dominant negatives. Expression of the mutants in cells lacking endogenous NRMT1 resulted in minimal accumulation of N‐terminal trimethylation, indicating homozygosity could help drive oncogenesis or serve as a marker for sensitivity to DNA damaging chemotherapeutics or γ‐irradiation.
Use of oxygen isotopes to differentiate between nitrous oxide produced by fungi or bacteria during denitrification
Authors: Rohe Lena , Well Reinhard , Lewicka‐Szczebak Dominika 
Published: May 2017

RationaleFungal denitrifiers can contribute substantially to N2O emissions from arable soil and show a distinct site preference for N2O (SP(N2O)). This study sought to identify another process‐specific isotopic tool to improve precise identification of N2O of fungal origin by mass spectrometric analysis of the N2O produced.MethodsThree pure bacterial and three fungal species were incubated under denitrifying conditions in treatments with natural abundance and stable isotope labelling to analyse the N2O produced. Combining different applications of isotope ratio mass spectrometry enabled us to estimate the oxygen (O) exchange accelerated by denitrifying enzymes and the ongoing microbial pathway in parallel. This experimental set‐up allowed the determination of δ18O(N2O) values and isotopic fractionation of O, as well as SP(N2O) values, as a perspective to differentiate between microbial denitrifiers.ResultsOxygen exchange during N2O production was lower for bacteria than for fungi, differed between species, and depended also on incubation time. Apparent O isotopic fractionation during denitrification was in a similar range for bacteria and fungi, but application of the fractionation model indicated that different enzymes in bacteria and fungi were responsible for O exchange. This difference was associated with different isotopic fractionation for bacteria and fungi.Conclusionsδ18O(N2O) values depend on isotopic fractionation and isotopic fractionation may differ between processes and organism groups. By comparing SP(N2O) values, O exchange and the isotopic signature of precursors, we propose here a novel tool for differentiating between different sources of N2O.
Large variability in CO2 and N2O emissions and in 15N site preference of N2O from reactions of nitrite with lignin and its derivatives at different pH
Authors: Wei Jing , Zhou Minghua , Vereecken Harry , Brüggemann Nicolas 
Published: May 2017

RationaleChemodenitrification is an important N2O source in soil; however, knowledge about the production of CO2 and N2O from abiotic nitrite‐SOM reactions, especially the N2O isotopic signatures (intramolecular 15N site preference (SP), and δ15Nbulk and δ18O values), is quite limited at present.MethodsN2O and CO2 emissions from chemical reactions of nitrite with lignin products were determined with gas chromatography, and their response surfaces as a function of pH from 3 to 6 and nitrite concentration from 0.1 to 0.5 mM were explored with polynomial regression. The intramolecular 15N distribution of N2O, as well as δ15Nbulk and δ18O values, were measured with an isotope ratio mass spectrometer coupled to an online pre‐concentration unit. The variability in N2O SP values was tested from pH 3 to 5, and for nitrite concentrations from 0.3 to 0.5 mM.ResultsBoth CO2 and N2O emissions varied largely with pH and the structure of lignin products. The highest N2O emission occurred at pH 4–5 in 4‐hydroxy‐3,5‐dimethoxybenzaldehyde and 4‐hydroxy‐3,5‐dimethoxybenzoic acid treatments, and at pH 3 in the treatments with lignin, 4‐hydroxy‐3‐methoxybenzaldehyde, 4‐hydroxy‐3‐methoxybenzoic acid, 4‐hydroxybenzaldehyde, and 4‐hydroxybenzoic acid. A wide range of N2O SP values (11.9–37.4‰), which was pH dependent and not distinguishable from microbial pathways, was observed at pH 3–5. The δ15Nbulk and δ18O values of N2O were both in a similar range to that reported for fungal denitrification and bacterial denitrification.ConclusionsThese results present the first characterization of the isotopic composition of N2O from chemodenitrification in pure chemical assays. Chemical reactions of nitrite with lignin are pH‐dependent and associated with substantial CO2 and N2O emissions. The SP values of N2O derived from chemodenitrification were neither distinguishable from the biotic pathways nor remained stable with varying pH. Therefore, the use of N2O isotopic signatures for source partitioning is restricted when chemodenitrification is contributing significantly to N2O emission.
Propofol (2,6‐diisopropylphenol) is an applicable immersion anesthetic in the axolotl with potential uses in hemodynamic and neurophysiological experiments
Authors: Thygesen Mathias Møller , Rasmussen Mikkel Mylius , Madsen Jesper Guldsmed , Pedersen Michael , Lauridsen Henrik 
Published: May 2017

AbstractThe Mexican axolotl (Ambystoma mexicanum) is an important model species in regenerative biology. Traditionally, axolotls are anesthetized using benzocaine or MS‐222, both of which act to inhibit voltage gated sodium channels thereby preventing action potential propagation. In some neurophysiological experiments this is not desirable; therefore we tested propofol as an alternative anesthetic in the axolotl. We evaluated benzocaine, MS‐222, and propofol's cardiovascular effects, effects on action potential propagation in the spinal cord, and gross limb regenerative effects. We found that propofol is applicable as a general anesthetic in the axolotl allowing for neurophysiological experiments and yielding a stable anesthesia with significantly less cardiovascular effect than both benzocaine and MS‐222. Additionally, propofol did not affect gross limb regeneration. In conclusion we suggest the consideration of propofol as an alternative immersion anesthetic to benzocaine and MS‐222.
Radiation search operations using scene understanding with autonomous UAV and UGV
Authors: Christie Gordon , Shoemaker Adam , Kochersberger Kevin , Tokekar Pratap , McLean Lance , Leonessa Alexander 
Published: May 2017

AbstractAutonomously searching for hazardous radiation sources requires the ability of the aerial and ground systems to understand the scene they are scouting. In this paper, we present systems, algorithms, and experiments to perform radiation search using unmanned aerial vehicles (UAV) and unmanned ground vehicles (UGV) by employing semantic scene segmentation. The aerial data are used to identify radiological points of interest, generate an orthophoto along with a digital elevation model (DEM) of the scene, and perform semantic segmentation to assign a category (e.g., road, grass) to each pixel in the orthophoto. We perform semantic segmentation by training a model on a dataset of images we collected and annotated, using the model to perform inference on images of the test area unseen to the model, and then refining the results with the DEM to better reason about category predictions at each pixel. We then use all of these outputs to plan a path for a UGV carrying a LiDAR to map the environment and avoid obstacles not present during the flight, and a radiation detector to collect more precise radiation measurements from the ground. Results of the analysis for each scenario tested favorably. We also note that our approach is general and has the potential to work for a variety of different sensing tasks.
Online covariance estimation for novelty‐based visual obstacle detection
Authors: Ross Patrick , English Andrew , Ball David 
Published: May 2017

AbstractRobust obstacle detection remains a challenge for mobile robots traversing outdoor field environments. Obstacle detection systems that combine multiple cues can potentially overcome deficiencies in individual cues. A key challenge in designing multi‐sensor obstacle detection systems is to automatically and appropriately combine these cues in an unsupervised manner. This paper presents a method for obstacle detection, which continuously adapts its obstacle definition and the weighting of each cue for the current conditions. The key contribution of this paper is a method for online covariance estimation for Parzen windows probability density estimation, which in this application determines the relative importance of each descriptor dimension. By iteratively estimating the covariance using small subsets of the available data, the proposed method is capable of converging to an approximate solution order of magnitude faster than standard optimizers, making it suitable for use online. The application of this covariance estimation method to our novelty‐based obstacle detection system improves obstacle detection precision and reduces learning duration after environmental transitions. It also removes all environment‐specific parameters from the method, and allows the descriptor to contain arbitrary data without time‐consuming hand‐tuning.
Bias and inference from misspecified mixed‐effect models in stepped wedge trial analysis
Authors: Thompson Jennifer A. , Fielding Katherine L. , Davey Calum , Aiken Alexander M. , Hargreaves James R. , Hayes Richard J. 
Published: May 2017

Many stepped wedge trials (SWTs) are analysed by using a mixed‐effect model with a random intercept and fixed effects for the intervention and time periods (referred to here as the standard model). However, it is not known whether this model is robust to misspecification.We simulated SWTs with three groups of clusters and two time periods; one group received the intervention during the first period and two groups in the second period. We simulated period and intervention effects that were either common‐to‐all or varied‐between clusters. Data were analysed with the standard model or with additional random effects for period effect or intervention effect. In a second simulation study, we explored the weight given to within‐cluster comparisons by simulating a larger intervention effect in the group of the trial that experienced both the control and intervention conditions and applying the three analysis models described previously.Across 500 simulations, we computed bias and confidence interval coverage of the estimated intervention effect.We found up to 50% bias in intervention effect estimates when period or intervention effects varied between clusters and were treated as fixed effects in the analysis. All misspecified models showed undercoverage of 95% confidence intervals, particularly the standard model. A large weight was given to within‐cluster comparisons in the standard model.In the SWTs simulated here, mixed‐effect models were highly sensitive to departures from the model assumptions, which can be explained by the high dependence on within‐cluster comparisons. Trialists should consider including a random effect for time period in their SWT analysis model. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
Competing‐risks model in screening for pre‐eclampsia in twin pregnancy according to maternal factors and biomarkers at 11–13 weeks' gestation
Authors: Francisco C. , Wright D. , Benkő Z. , Syngelaki A. , Nicolaides K. H. 
Published: May 2017

ABSTRACTObjectiveTo develop a model for screening for pre‐eclampsia (PE) in twin pregnancies based on maternal demographic characteristics and medical history and biomarkers at 11–13 weeks' gestation.MethodsThis was a screening study in twin pregnancies at 11–13 weeks' gestation. Bayes theorem was used to combine the a‐priori risk from maternal factors with various combinations of uterine artery pulsatility index (UtA‐PI), mean arterial pressure (MAP), serum pregnancy‐associated plasma protein‐A (PAPP‐A) and placental growth factor (PlGF) multiples of the median (MoM) values. The performance of screening for PE requiring delivery at < 32, < 37 and < 42 weeks' gestation was estimated in 1100 twin pregnancies and 35 948 singleton pregnancies with complete data on UtA‐PI, MAP, PlGF and PAPP‐A.ResultsIn twin pregnancies that developed PE, the values of MAP and UtA‐PI were increased and the values of PlGF and PAPP‐A were decreased. The distributions of log10 MoM values of biomarkers with gestational age at delivery were similar to those that were previously reported in singleton pregnancies and it was therefore assumed that the same model could be used for both singleton and twin pregnancies. The performance of screening for PE by maternal factors was improved by the addition of MAP, UtA‐PI and PlGF; there was no further improvement with the addition of PAPP‐A. In a mixed population of singleton and twin pregnancies, combined screening by maternal factors, MAP, UtA‐PI and PlGF and risk cut‐off of 1 in 75 for PE at < 37 weeks, the detection rate of PE at < 32, < 37 and < 42 weeks in singleton pregnancies was 91%, 77% and 57%, respectively, at a screen‐positive rate (SPR) of 13%; the respective rates for twin pregnancies were 100%, 99% and 97%, at a SPR of 75%.ConclusionFirst‐trimester combined screening for PE in singleton pregnancies can be adapted for screening in twins, leading to detection of nearly all affected cases but at a high SPR. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta‐analysis
Authors: Srebniak M. I. , Joosten M. , Knapen M. F. C. M. , Arends L. R. , Polak M. , van Veen S. , Go A. T. J. I. , Van Opstal D. 
Published: May 2017

ABSTRACTObjectiveTo establish, based on a systematic literature review, the frequency of pathogenic submicroscopic chromosomal aberrations in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, with the aim of determining whether high‐resolution testing for submicroscopic aberrations is beneficial in a general pregnant population.MethodsEMBASE, PubMed, Web of Science and CENTRAL databases were searched systematically on 3 June 2016 for all relevant articles on the prevalence of pathogenic submicroscopic copy number variants (CNVs) in fetuses referred for prenatal invasive testing because of advanced maternal age (AMA) or parental anxiety (ANX). Relevant full‐text articles were analyzed and the prevalence of submicroscopic CNVs was calculated based on the extracted data. Meta‐analysis was conducted in a pooled cohort of 10 614 fetuses based on the 10 largest studies (n > 300) of a total of 19 that were relevant.ResultsPooled estimate analysis indicated that 0.84% (95% CI, 0.55–1.30%) of fetuses that had invasive testing because of AMA/ANX carried a pathogenic clinically significant submicroscopic aberration. The onset/penetrance of submicroscopic findings was studied in 10 314 fetuses reported in eight papers that presented aberrant cases with all necessary details to allow assessment of the findings. The pooled estimates resulting from meta‐analysis of the data indicated that an early‐onset syndromic disorder was detected in 0.37% (95% CI, 0.27–0.52%) of cases, a susceptibility CNV was found in 0.30% (95% CI, 0.14–0.67%) and late‐onset diseases were reported in 0.11% (95% CI, 0.05%–0.21%). The prevalence of early‐onset syndromic disorders caused by a submicroscopic aberration was calculated to be 1:270. When the risk for submicroscopic aberrations is added to the individual risk for microscopic chromosomal aberrations, all pregnant women have a risk of higher than 1 in 180 for a relevant chromosomal aberration, and pregnant women under 36 years of age have a higher risk for submicroscopic pathogenic aberrations than for Down syndrome.ConclusionThis systematic review shows that a significant proportion of fetuses in a general pregnant population carry a submicroscopic pathogenic CNV. Based on these figures, all women should be informed on their individual risk for all pathogenic chromosomal aberrations and not only for common trisomies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Decreased endothelial function and increased subclinical heart failure in women several years after pre‐eclampsia
Authors: Breetveld N. M. , Ghossein‐Doha C. , van Neer J. , Sengers M. J. J. M. , Geerts L. , van Kuijk S. M. J. , van Dijk A. P. , van der Vlugt M. J. , Heidema W. M. , Brunner‐La Rocca H. P. , Scholten R. R. , Spaanderman M. E. A. 
Published: May 2017

ABSTRACTObjectivesPre‐eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure Stage B (HF‐B). In this study, we assessed the relationship between endothelial function, measured by flow‐mediated dilation (FMD), and HF‐B in women with a history of PE.MethodsThis was an observational study in which 67 formerly pre‐eclamptic women (≥ 4 years postpartum) and 37 healthy parous controls were assessed ultrasonographically for cardiac function and geometry, as well as for endothelial function by means of brachial artery FMD. HF‐B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Cardiovascular and metabolic syndrome variables were compared between women with history of PE and controls, as well as between those in the formerly pre‐eclamptic group who had HF Stage A, HF‐B or no HF. Logistic regression analysis was performed to assess the associations of FMD with PE, metabolic syndrome risk factors and obstetric parameters.ResultsThe prevalence of HF‐B amongst formerly pre‐eclamptic women was three‐fold higher than that observed for controls (25% vs 8%, P < 0.05), while FMD was lower in formerly pre‐eclamptic women compared with controls (6.12% vs 8.22%, P < 0.01); history of PE remained associated independently with lower FMD after adjusting for metabolic syndrome risk factors and obstetric parameters (β, –1.88; 95% CI, −3.59 to −0.18). However, HF‐B did not relate to low FMD in formerly pre‐eclamptic women.ConclusionsYears after pregnancy, formerly pre‐ eclamptic women have lower FMD and have HF‐B more often compared with healthy parous controls. Nonetheless, HF‐B was not related to reduced FMD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Quantified discordant placental echogenicity in twin anemia–polycythemia sequence (TAPS) and middle cerebral artery peak systolic velocity
Authors: Bamberg C. , Diemert A. , Glosemeyer P. , Hecher K. 
Published: May 2017

ABSTRACTObjectiveTo quantify sonographic placental echogenicity in twin anemia–polycythemia sequence (TAPS) and to correlate it with middle cerebral artery peak systolic velocity (MCA‐PSV) measurements.MethodsWe performed a retrospective search for consecutive TAPS cases between 16 and 36 weeks of gestation (MCA‐PSV > 1.5 multiples of the median (MoM) in the anemic donor and < 1.0 MoM in the polycythemic recipient) in our database of monochorionic twin gestations from January 2007 until December 2016. In cases for which ultrasound images showing the donor's and the recipient's part of the placenta were available, echogenicity for both twins was quantified by image processing. MCA‐PSV Doppler values of both fetuses were correlated to their respective placental echogenicity. Placental thickness of both twins was also measured.ResultsOf 756 cases with MCA‐PSV measurements identified from the database, 36 (4.8%) had TAPS; of these, 23 had TAPS combined with twin–twin transfusion syndrome and 13 showed isolated TAPS. Placental echogenicity could be quantified in 28 pregnancies. Mean ± SD placental echogenicity of donor twins was significantly higher than that of recipients (138.7 ± 22.8 vs 77.9 ± 37.0; P < 0.0001). Furthermore, a significant positive correlation was found between placental echogenicity and MCA‐PSV MoM (R = 0.67, P < 0.0001). Mean placental thickness of donor twins (n = 20) was significantly higher than that of recipients (49.3 mm ± 13.4 vs 25.4 mm ± 10.1; P < 0.0001).ConclusionsEchogenicity of the placental share in recipient and donor twins with TAPS correlates with MCA‐PSV values. Quantification of sonographic placental echogenicity may help to determine the severity of TAPS in monochorionic twins. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase
Authors: Steegmann Juan Luis , Colomer Dolors , Gómez-Casares Maria-Teresa , García-Gutiérrez Valentín , Ortí Guillermo , Ramírez-Payer Angel , Olavarria Eduardo , Vall-llovera Ferrán , Giraldo Pilar , Conde Eulogio , Vallansot Rolando , López-Lorenzo Jose Luis , Palomera Luis , Álvarez-Larrán Alberto , Conesa Venancio , Bautista Guiomar , Casas Laura , Giles Frank , Hochhaus Andreas , Casado-Montero Luis Felipe 
Published: May 2017

Abstract

Purpose
This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter.

Methods
This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter).

Results
The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months.

Conclusions
The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.