julilili42/papers huggingface dataset:
Design, Synthesis and Biological Evaluation of 7 Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3β inhibitors
2019-05-22

The dataset related to the publication: Andreev et al. Design, Synthesis and Biological Evaluation of 7 Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3β inhibitors.<br> <br> The files include: 1) Movies of the MD simulations of compounds 14b (<strong>Cmpd14b.mpg</strong>) and 24 (<strong>Cmpd24.mpg</strong>). 2) Raw trajectory files of the Desmond MD simulations of the compounds 14b (<strong>14b.zip</strong>) and 24 (<strong>24.zip</strong>) (contains out.cms and the full trj files). 3) Output conformations of the QM Tautomer &amp; Conformation Predictor of Maestro (Schrödinger, LLC, New York, NY, 2019) of the compounds 14b (<strong>Cmpd14b_QMconftauto_output.mae</strong>; <strong>Cmpd14b_QMconftauto_output.sdf</strong>) and 24 (<strong>Cmpd24_QMconftauto_output.mae</strong>; <strong>Cmpd24_QMconftauto_output.sdf</strong>) 4) Jaguar pKa calculation (conformations) output-files for compounds 14b, 14c, 14d, 14e, 14f, 14g, 14h, 14i, 14j, 14k, 14l, 14m, 14n <strong>pKa.zip</strong> (contains conformation in .mae file and Final weighted pKa value in .out file).
Cyclotron emission, absorption, and the two faces of X-ray pulsar A 0535+262
2019-05-23

Abstract Deep NuSTAR observation of X-ray pulsar A 0535+262, performed at a very low luminosity of ∼7 × 1034 erg s−1, revealed the presence of two spectral components. We argue that the high-energy component is associated with cyclotron emission from recombination of electrons collisionally excited to the upper Landau levels. The cyclotron line energy of Ecyc = 47.7 ± 0.8 keV was measured at the luminosity of almost an order of magnitude lower than what was achieved before. The data firmly exclude a positive correlation of the cyclotron energy with the mass accretion rate in this source.
Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro
2019-05-23

Ivermectin is the drug of choice for many parasitic infections, with more than one billion doses being distributed in onchocerciasis programs. The drug has been put into focus recently by the malaria community because of its potential to kill blood-sucking mosquitoes, thereby reducing malaria transmission.
Isocaloric Substitution of Dietary Carbohydrate Intake with Fat Intake and MRI-Determined Total Volumes of Visceral, Subcutaneous and Hepatic Fat Content in Middle-Aged Adults
2019-05-23

The present study investigated the association of carbohydrate intake and isocaloric substitution with different types of fat with visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat content as determined by magnetic resonance imaging (MRI). Data from 283 participants (mean age 56.1 ± 9.0 years) from the MRI sub study of the KORA FF4 study were included. VAT, SAT and total body fat were quantified by a volume-interpolated VIBE-T1w-Dixon MR sequence. Hepatic fat content was determined as the proton density fat-fraction (PDFF) derived from multiecho-T1w MR sequence. Dietary intake was estimated using information provided by two different instruments, that is, repeated 24-h food lists and a food frequency questionnaire. Replacing total carbohydrates with an isoenergetic amount of total fat was significantly positively associated with VAT and hepatic fat, while there was no significant association with SAT. The multivariable adjusted β-coefficient for replacing 5% of total energy (5E%) carbohydrates with total fat was 0.42 L (95% CI: 0.04, 0.79) for VAT. A substitution in total fat intake by 5E% was associated with a significant increase in liver fat content by 23% (p-value 0.004). If reproduced in prospective studies, such findings would strongly argue for limiting dietary fat intake.
The Diversity of Plant Small RNAs Silencing Mechanisms
2019-05-23

Small RNAs gene regulation was first discovered about 20 years ago. It represents a conserve gene regulation mechanism across eukaryotes and is associated to key regulatory processes. In plants, small RNAs tightly regulate development, but also maintain genome stability and protect the plant against pathogens. Small RNA gene regulation in plants can be divided in two canonical pathways: Post-transcriptional Gene Silencing (PTGS) that results in transcript degradation and/or translational inhibition or Transcriptional Gene Silencing (TGS) that results in DNA methylation. In this review, we will focus on the model plant Arabidopsis thaliana. We will provide a brief overview of the molecular mechanisms involved in canonical small RNA pathways as well as introducing more atypical pathways recently discovered.
Factors influencing the complication rate in pediatric supracondylar humerus fractures
2019-05-23

The aim of the study was to identify influencing factors on the complication rate in pediatric supracondylar humerus fractures (PSHF). 22 male and 19 female patients with an extension type PSHF underwent conservative and operative treatment at a single trauma department and were reviewed retrospectively. The complications were assessed and the groups of patients with and without complications were compared according to patient- and therapy-related factors. The overall complication rate was 19.5%. Two patients had a primary and 4 patients a postoperative neurological deficit. One patient developed a pin infection after open reduction and crossed pin fixation. One patient underwent early revision surgery because of insufficient initial reduction after closed reduction and crossed pin fixation. All complications appeared in the surgical treatment group. The appearance of complications was significantly associated with a higher Gartland stage. The median time between trauma and operation was significantly longer in patients without compared to patients with complications. PSHF are associated with a high rate of neurological complications. The Gartland stage and the necessity of surgical treatment are the major influencing factors on the complication rate.
Surgery of the lateral skull base: a 50-year endeavour
2019-05-24

Disregarding the widely used division of skull base into anterior and lateral, since the skull base should be conceived as a single anatomic structure, it was to our convenience to group all those approaches that run from the antero-lateral, pure lateral and postero-lateral side of the skull base as “Surgery of the lateral skull base”. “50 years of endeavour” points to the great effort which has been made over the last decades, when more and more difficult surgeries were performed by reducing morbidity. The principle of lateral skull base surgery, “remove skull base bone to approach the base itself and the adjacent sites of the endo-esocranium”, was then combined with function preservation and with tailoring surgery to the pathology. The concept that histology dictates the extent of resection, balancing the intrinsic morbidity of each approach was the object of the first section of the present report. The main surgical approaches were described in the second section and were conceived not as a step-by-step description of technique, but as the highlighthening of the surgical principles. The third section was centered on open issues related to the tumor and its treatment. The topic of vestibular schwannoma was investigated with the current debate on observation, hearing preservation surgery, hearing rehabilitation, radiotherapy and the recent efforts to detect biological markers able to predict tumor growth. Jugular foramen paragangliomas were treated in the frame of radical or partial surgery, radiotherapy, partial “tailored” surgery and observation. Surgery on meningioma was debated from the point of view of the neurosurgeon and of the otologist. Endolymphatic sac tumors and malignant tumors of the external auditory canal were also treated, as well as chordomas, chondrosarcomas and petrous bone cholesteatomas. Finally, the fourth section focused on free-choice topics which were assigned to aknowledged experts. The aim of this work was attempting to report the state of the art of the lateral skull base surgery after 50 years of hard work and, above all, to raise questions on those issues which still need an answer, as to allow progress in knowledge through sharing of various experiences. At the end of the reading, if more doubts remain rather than certainties, the aim of this work will probably be achieved.
Early positive effects of tree species richness on soil organic carbon accumulation in a large-scale forest biodiversity experiment
2019-05-24

Abstract Aims Tree species richness has been reported to have positive effects on aboveground biomass and productivity, but little is known about its effects on soil organic carbon (SOC) accumulation. Methods To close this gap, we made use of a large biodiversity–ecosystem functioning experiment in subtropical China (BEF-China) and tested whether tree species richness enhanced SOC accumulation. In 2010 and 2015, vertically layered soil samples were taken to a depth of 30 cm from 57 plots ranging in tree species richness from one to eight species. Least squares-based linear models and analysis of variance were used to investigate tree diversity effects. Structural equation modeling was used to explore hypothesized indirect relationships between tree species richness, leaf-litter biomass, leaf-litter carbon content, fine-root biomass and SOC accumulation. Important Findings Overall, SOC content decreased by 5.7 and 1.1 g C kg−1 in the top 0–5 and 5–10 cm soil depth, respectively, but increased by 1.0 and 1.5 g C kg−1 in the deeper 10–20 and 20–30 cm soil depth, respectively. Converting SOC content to SOC stocks using measures of soil bulk density showed that tree species richness did enhance SOC accumulation in the different soil depths. These effects could only to some extent be explained by leaf-litter biomass and not by fine-root biomass. Our findings suggest that carbon storage in new forests in China could be increased by planting more diverse stands, with the potential to contribute to mitigation of climate warming.
Brain State-dependent Gain Modulation of Corticospinal Output in the Active Motor System
2019-05-24

Abstract The communication through coherence hypothesis suggests that only coherently oscillating neuronal groups can interact effectively and predicts an intrinsic response modulation along the oscillatory rhythm. For the motor cortex (MC) at rest, the oscillatory cycle has been shown to determine the brain’s responsiveness to external stimuli. For the active MC, however, the demonstration of such a phase-specific modulation of corticospinal excitability (CSE) along the rhythm cycle is still missing. Motor evoked potentials in response to transcranial magnetic stimulation (TMS) over the MC were used to probe the effect of cortical oscillations on CSE during several motor conditions. A brain–machine interface (BMI) with a robotic hand orthosis allowed investigating effects of cortical activity on CSE without the confounding effects of voluntary muscle activation. Only this BMI approach (and not active or passive hand opening alone) revealed a frequency- and phase-specific cortical modulation of CSE by sensorimotor beta-band activity that peaked once per oscillatory cycle and was independent of muscle activity. The active MC follows an intrinsic response modulation in accordance with the communication through coherence hypothesis. Furthermore, the BMI approach may facilitate and strengthen effective corticospinal communication in a therapeutic context, for example, when voluntary hand opening is no longer possible after stroke.
Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites
2019-05-24

<b>Introduction:</b> The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant <i>CYP2D6</i> alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different <i>CYP2D6</i> genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1). <b>Materials and Methods:</b> Using TaqMan<sup>®</sup> assays common alleles of <i>CYP2D6</i> (<sup>∗</sup>1, <sup>∗</sup>2, <sup>∗</sup>4, <sup>∗</sup>5, <sup>∗</sup>6, <sup>∗</sup>10, <sup>∗</sup>17, and <sup>∗</sup>41) and gene duplication were identified in 134 breast cancer patients. Based on <i>CYP2D6</i> genotypes patients with an activity score 1 (<i>n</i> = 15) and 0-0.5 (<i>n</i> = 2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/day, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology. <b>Results:</b> At baseline, (Z)-endoxifen plasma concentrations (33 ± 15.5, 28.1 ± 14, 26.6 ± 23.4, 14.3 ± 8.6, and 10.7 ± 5.5 nmol/l for EM/EM, EM/IM, EM/PM, IM/IM and PM/PM, respectively) and the metabolic ratio (Z)-Endoxifen/N-desmethyltamoxifen (0.0558 ± 0.02, 0.0396 ± 0.0111, 0.0332 ± 0.0222, 0.0149 ± 0.0026, and 0.0169 ± 0.0177 for EM/EM, EM/IM, EM/PM, IM/IM, and PM/PM, respectively) correlated with <i>CYP2D6</i> genotype (Kruskal-Wallis <i>p</i> = 0.013 and <i>p</i> < 0.0001, respectively). Dose escalation to 30 and 40 mg/day in patients with a CYP2D6 activity score of 1 (<i>n</i> = 15) and 0-0.5 (<i>n</i> = 2) resulted in a significant increase in (Z)-endoxifen plasma levels (22.17 ± 24.42, 34.43 ± 26.54, and 35.77 ± 28.89 nmol/l at baseline, after 4 and 8 months, respectively, Friedman <i>p</i> = 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. No severe side effects were recorded during dose escalation. <b>Conclusion:</b> For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen.
Arterial wall contrast enhancement in progressive moyamoya disease
2019-05-24

OBJECTIVE The purpose of this study was to evaluate chronological patterns of arterial wall contrast enhancement in contrast-enhanced high-resolution MRI (CE-HR-MRI) in patients with moyamoya disease (MMD). METHODS The authors performed a blinded analysis of clinical and imaging data from MMD patients. Data were analyzed chronologically for each patient and the intensity of arterial wall enhancement was correlated with the clinical and imaging-based progression status of the disease. RESULTS A total of 31 MMD patients and 61 imaging time points were included. CE-HR-MRI results were available for 56 time points, representing 112 hemispheric analyses. No arterial wall contrast enhancement (grade 1) was seen in 54 (48%) of the analyses, mild enhancement (grade 2) in 24 (21%), moderate enhancement (grade 3) in 15 (13%), and strong (grade 4) mainly concentric arterial wall contrast enhancement in 19 (17%). Grade 4 contrast enhancement was significantly (p &lt; 0.001) associated with clinical disease progression within 6 months (before or after the MRI) compared to grades 1–3, with positive and negative predictive values of 0.8 and 0.88, respectively. Grades 1 and 2 (no contrast enhancement and only mild contrast enhancement) were highly predictive for stable disease (negative predictive value: 0.95). CONCLUSIONS A specific chronological increasing and decreasing pattern of arterial wall contrast enhancement associated with “beginning” as well as progression of angiopathy occurs in MMD patients. In clinical practice, CE-HR-MRI of the arterial wall may help to identify patients at risk of new strokes caused by disease progression and hence impel early treatment for future stroke prevention. Understanding of this temporary enhancement of the arterial wall might also bring new insights into the etiology of MMD.
Evidence for the radiation-pressure dominated accretion disk in bursting pulsar GRO J1744−28 using timing analysis
2019-05-24

The X-ray pulsar GRO J1744−28 is a unique source that shows both pulsations and type-II X-ray bursts, allowing studies of the interaction of the accretion disk with the magnetosphere at huge mass-accretion rates exceeding 10 19 g s −1 during its super-Eddington outbursts. The magnetic field strength in the source, B ≈ 5 × 10 11 G, is known from the cyclotron absorption feature discovered in the energy spectrum around 4.5 keV. Here, we have explored the flux variability of the source in context of interaction of its magnetosphere with the radiation-pressure dominated accretion disk. Specifically, we present the results of the analysis of noise power density spectra (PDS) using the observations of the source in 1996–1997 by the Rossi X-ray Timing Explorer (RXTE). Accreting compact objects commonly exhibit a broken power-law PDS shape with a break corresponding to the Keplerian orbital frequency of matter at the innermost disk radius. The observed frequency of the break can thus be used to estimate the size of the magnetosphere. We find, however, that the observed PDS of GRO J1744−28 differs dramatically from the canonical shape. The observed break frequency appears to be significantly higher than expected based on the magnetic field estimated from the cyclotron line energy. We argue that these observational facts can be attributed to the existence of the radiation-pressure dominated region in the accretion disk at luminosities above ∼2 × 10 37 erg s −1 . We discuss a qualitative model for the PDS formation in such disks, and show that its predictions are consistent with our observational findings. The presence of the radiation-pressure dominated region can also explain the observed weak luminosity dependence of the inner radius, and we argue that the small inner radius can be explained by a quadrupole component dominating the magnetic field of the neutron star.
An arbitrary-spectrum spatial visual stimulator for vision research
2019-05-24

Abstract Visual neuroscientists require accurate control of visual stimulation. However, few stimulator solutions simultaneously offer high spatio-temporal resolution and free control over the spectra of the light sources, because they rely on off-the-shelf technology developed for human trichromatic vision. Importantly, consumer displays fail to drive UV-shifted short wavelength-sensitive photoreceptors, which strongly contribute to visual behaviour in many animals, including mice, zebrafish and fruit flies. Moreover, many non-mammalian species feature more than three spectral photoreceptor types. Here, we present a flexible, spatial visual stimulator with up to 6 arbitrary spectrum chromatic channels. It combines a standard digital light processing engine with open source hard- and software that can be easily adapted to the experimentalist’s needs. We demonstrate the capability of this general visual stimulator experimentally in the in vitro mouse retinal whole-mount and the in vivo zebrafish. Hereby, we intend starting a community effort of sharing and developing a common stimulator design.
Comparison of CFD Simulation to UAS Measurements for Wind Flows in Complex Terrain: Application to the WINSENT Test Site
2019-05-24

This investigation presents a modelling strategy for wind-energy studies in complex terrains using computational fluid dynamics (CFD). A model, based on an unsteady Reynolds Averaged Navier-Stokes (URANS) approach with a modified version of the standard k-ε model, is applied. A validation study based on the Leipzig experiment shows the ability of the model to simulate atmospheric boundary layer characteristics such as the Coriolis force and shallow boundary layer. By combining the results of the model and a design of experiments (DoE) method, we could determine the degree to which the slope, the leaf area index, and the forest height of an escarpment have an effect on the horizontal velocity, the flow inclination angle, and the turbulent kinetic energy at critical positions. The DoE study shows that the primary contributor at a turbine-relevant height is the slope of the escarpment. In the second step, the method is extended to the WINSENT test site. The model is compared with measurements from an unmanned aircraft system (UAS). We show the potential of the methodology and the satisfactory results of our model in depicting some interesting flow features. The results indicate that the wakes with high turbulence levels downstream of the escarpment are likely to impact the rotor blade of future wind turbines.
CIELO-RGS: a catalog of soft X-ray ionized emission lines
2019-05-24

\\nContext. High-resolution X-ray spectroscopy has advanced our understanding of the hot Universe by revealing physical properties like kinematics, temperature, and abundances of the astrophysical plasmas. Despite technical and scientific achievements, the lack of scientific products at a level higher than count spectra is hampering complete scientific exploitation of high-quality data. This paper introduces the Catalog of Ionized Emission Lines Observed by the Reflection Grating Spectrometer (CIELO-RGS) onboard the XMM-Newton space observatory.\\nAims. The CIELO-RGS catalog aims to facilitate the exploitation of emission features in the public RGS spectra archive. In particular, we aim to analyze the relationship between X-ray spectral diagnostics parameters and measurements at other wavelengths. This paper focuses on the methodology of catalog generation, describing the automated line-detection algorithm.\\nMethods. A moderate sample (∼2400 observations) of high-quality RGS spectra available at XMM-Newton Science Archive is used as our starting point. A list of potential emission lines is selected based on a multi-scale peak-detection algorithm in a uniform and automated way without prior assumption on the underlying astrophysical model. The candidate line list is validated via spectral fitting with simple continuum and line profile models. We also compare the catalog content with published literature results on a small number of exemplary sources.\\nResults. We generate a catalog of emission lines (1.2 × 104) detected in ∼1600 observations toward stars, X-ray binaries, supernovae remnants, active galactic nuclei, and groups and clusters of galaxies. For each line, we report the observed wavelength, broadening, energy and photon flux, equivalent width, and so on.\\n
Boosted Density Estimation Remastered
2019-05-24

There has recently been a steady increase in the number iterative approaches to density estimation. However, an accompanying burst of formal convergence guarantees has not followed; all results pay the price of heavy assumptions which are often unrealistic or hard to check. The Generative Adversarial Network (GAN) literature --- seemingly orthogonal to the aforementioned pursuit --- has had the side effect of a renewed interest in variational divergence minimisation (notably -GAN). We show that by introducing a weak learning assumption (in the sense of the classical boosting framework) we are able to import some recent results from the GAN literature to develop an iterative boosted density estimation algorithm, including formal convergence results with rates, that does not suffer the shortcomings other approaches. We show that the density fit is an exponential family, and as part of our analysis obtain an improved variational characterisation of -GAN.