julilili42/papers huggingface dataset:
Inter- and intra-observer variability of an anatomical landmark-based, manual segmentation method by MRI for the assessment of skeletal muscle fat content and area in subjects from the general population
2018-04-16

From 50 subjects included (mean age 56.1 ± 8.8 years, 60.0% males, mean body mass index 28.3 ± 5.2) 2'400 measurements were obtained. Interobserver agreement was excellent for all muscle compartments (PDFF: ICC0.99, CSA: ICC0.98) with only minor absolute and relative differences (-0.2 ± 0.5%, 31 ± 44.7 mm<sup>2</sup>; -2.6 ± 6.4% and 2.7 ± 3.9%, respectively). Intra-observer reproducibility was similarly excellent (PDFF: ICC1.0, 0.0 ± 0.4%, 0.4%; CSA: ICC1.0, 5.5 ± 25.3 mm<sup>2</sup>, 0.5%, absolute and relative differences, respectively). All agreement was independent of age, gender, body mass index, body height and visceral adipose tissue (ICC0.96-1.0). Furthermore, PDFF reproducibility was independent of CSA (ICC0.93-0.99). Conclusions: Quantification of skeletal muscle fat content and area by MRI using an anatomical landmark-based, manual skeletal muscle segmentation is highly reproducible. Advances in knowledge: An anatomical landmark-based, manual skeletal muscle segmentation provides high reproducibility of skeletal muscle fat content and area and may therefore serve as a robust proxy for myosteatosis and sarcopenia in large cohort studies.
A subgroup of pleural mesothelioma expresses ALK protein and may be targetable by combined rapamycin and crizotinib therapy
2018-04-16

Malignant pleural mesothelioma (MPM) is a neoplasm with inferior prognosis and notorious chemotherapeutic resistance. Targeting aberrantly overexpressed kinases to cure MPM is a promising therapeutic strategy. Here, we examined ALK, MET and mTOR as potential therapeutic targets and determined the combinatorial efficacy of ALK and mTOR targeting on tumor cell growth <i>in vivo</i>. First, <i>ALK</i> overexpression, rearrangement and mutation were studied in primary MPM by qRT-PCR, FISH, immunohistochemistry and sequence analysis; <i>mTOR</i> and <i>MET</i> expression by qRT-PCR and immunohistochemistry. Overexpression of full-length <i>ALK</i> transcripts was observed in 25 (19.5%) of 128 primary MPM, of which ten expressed ALK protein. <i>ALK</i> overexpression was not associated with gene rearrangement, amplification or kinase-domain mutation. mTOR protein was detected in 28.7% MPM, co-expressed with ALK or MET in 5% and 15% MPM, respectively. The ALK/MET inhibitor crizotinib enhanced the anti-tumor effect of the mTOR-inhibitor rapamycin in a patient-derived MPM xenograft with co-activated ALK/mTOR: combined therapy achieved tumor shrinkage in 4/5 tumors and growth stagnation in one tumor. Treatment effects on proliferation, apoptosis, autophagy and pathway signaling were assessed using Ki-67 immunohistochemistry, TUNEL assay, LC3B immunofluorescence, and immunoblotting. Co-treatment significantly suppressed cell proliferation and induced autophagy and caspase-independent, necrotic cell death. Rapamycin/crizotinib simultaneously inhibited mTORC1 (evidenced by S6 kinase and RPS6 dephosphorylation) and ALK signaling (ALK, AKT, STAT3 dephosphorylation), and crizotinib suppressed the adverse AKT activation induced by rapamycin. In conclusion, co-treatment with rapamycin and crizotinib is effective in suppressing MPM tumor growth and should be further explored as a therapeutic alternative in mesothelioma.
Sparse reduced-rank regression for exploratory visualization of paired multivariate datasets
2018-04-16

Abstract In genomics, transcriptomics, and related biological fields (collectively known as omics ), it is common to work with n ≪ p datasets with the dimensionality much larger than the sample size. In recent years, combinations of experimental techniques began to yield multiple sets of features for the same set of biological replicates. One example is Patch-seq, a method combining single-cell RNA sequencing with electrophysiological recordings from the same cells. Here we present a framework based on sparse reduced-rank regression for obtaining an interpretable visualization of the relationship between the transcriptomic and the electrophysiological data. We use an elastic net regularization penalty that yields sparse solutions and allows for an efficient computational implementation. Using several publicly available Patch-seq datasets, we show that sparse reduced-rank regression outperforms both sparse full-rank regression and non-sparse reduced-rank regression in terms of predictive performance, and can outperform existing methods for sparse partial least squares and sparse canonical correlation analysis in terms of out-of-sample correlations. We introduce a bibiplot visualization in order to display the dominant factors determining the relationship between transcriptomic and electrophysiological properties of neurons. We believe that sparse reduced-rank regression can provide a valuable tool for the exploration and visualization of paired multivariate datasets, including Patch-seq.
The elastic wave equation and the stable numerical coupling of its interior and exterior problems
2018-04-16

Abstract We consider the elastic wave equation in three dimensions with transparent boundary conditions on a bounded, not necessarily convex domain. This leads to a coupling of the elastic wave equation in the interior domain with time‐dependent boundary integral equations. This coupled system is to be solved numerically. The major theoretical result of this paper shows a coercivity property of a Calderón operator for the elastic Helmholtz equation, which is valid for all complex frequencies in a half‐plane. Combining Laplace transform and energy techniques, this coercivity in the frequency domain is used to prove the stability of the fully discrete numerical method in the time domain. The considered numerical method couples finite elements and explicit leapfrog time‐stepping in the interior with boundary elements and convolution quadrature on the boundary. We present convergent error bounds for the semi‐ and full discretization.
Quasinormal modes of massive fermions in Kerr spacetime: Long-lived modes and the fine structure
2018-04-17

Quasinormal modes of a massive Dirac field were calculated for various static\\nblack hole backgrounds with the help of the WKB formula. These estimations,\\nhowever, are rough and valid only for very small values of , where \\nand are mass of the black hole and field respectively. Thus, no accurate\\ncalculations of massive Dirac modes are known even for the Schwarzschild black\\nhole and this is all the more so for the Kerr solution. Here we calculate\\nquasinormal modes of a massive Dirac field in the Kerr background. We have\\nshown that the infinitely long-lived quasinormal modes (quasiresonances), which\\nexist for boson fields, appear also in the fermions' quasinormal spectrum. Two\\nchiralities of massive fermions lead to an additional "fine structure" in the\\nspectrum. We discuss the effect of this fine structure on the behavior of\\nquasiresonances and the stability. The analysis is also extended to a charged\\nmassive field in the Kerr-Newman background.\\n
Particle accretion onto planets in discs with hydrodynamic turbulence
2018-04-17

The growth process of protoplanets can be sped up by accreting a large number of solid, pebble-sized objects that are still present in the protoplanetary disc. It is still an open question on how efficient this process works in realistic turbulent discs. We investigate the accretion of pebbles in turbulent discs that are driven by the purely hydrodynamical vertical shear instability (VSI). For this purpose, we performed global 3D simulations of locally isothermal, VSI turbulent discs that have embedded protoplanetary cores from 5 to 100 M ⊕ , which are placed at 5.2 au distance from the star. In addition, we followed the evolution of a swarm of embedded pebbles of different sizes under the action of drag forces between gas and particles in this turbulent flow. Simultaneously, we performed a set of comparison simulations for laminar viscous discs where the particles experience stochastic kicks. For both cases, we measured the accretion rate onto the cores as a function of core mass and Stokes number ( τ s ) of the particles and compared these values to recent magneto-rotational instability (MRI) turbulence simulations. Overall the dynamic is very similar for the particles in the VSI turbulent disc and the laminar case with stochastic kicks. For small mass planets (i.e. 5–10 M ⊕ ), well-coupled particles with τ s = 1, which have a size of about 1 m at this location, we find an accretion efficiency (rate of particles accreted over drifting inwards) of about 1.6−3%. For smaller and larger particles, this efficiency is higher. However, the fast inwards drift for τ s = 1 particles makes them the most effective for rapid growth, leading to mass doubling times of about 20 000 yr. For masses between 10 and 30 M ⊕ the core reaches the pebble isolation mass and the particles are trapped at the pressure maximum just outside of the planet, shutting off further particle accretion.
Genetics of brain age suggest an overlap with common brain disorders
2018-04-17

Numerous genetic and environmental factors contribute to psychiatric disorders and other brain disorders. Common risk factors likely converge on biological pathways regulating the optimization of brain structure and function across the lifespan. Here, using structural magnetic resonance imaging and machine learning, we estimated the gap between brain age and chronological age in 36,891 individuals aged 3 to 96 years, including individuals with different brain disorders. We show that several disorders are associated with accentuated brain aging, with strongest effects in schizophrenia, multiple sclerosis and dementia, and document differential regional patterns of brain age gaps between disorders. In 16,269 healthy adult individuals, we show that brain age gap is heritable with a polygenic architecture overlapping those observed in common brain disorders. Our results identify brain age gap as a genetically modulated trait that offers a window into shared and distinct mechanisms in different brain disorders.
Layered Carbodiimides A2M(CN2)3 with Tetravalent Cations M = Sn, Zr, and Hf
2018-04-17

The ternary carbodiimides Li 2 Sn(CN 2 ) 3 , Na 2 Sn(CN 2 ) 3 , Li 2 Zr(CN 2 ) 3 and Li 2 Hf(CN 2 ) 3 were synthesized and their crystal structures were solved and refined by means of powder X‐ray diffraction [Li 2 Zr(CN 2 ) 3 and Li 2 Hf(CN 2 ) 3 crystallize in R 3 c , whereas Li 2 Sn(CN 2 ) 3 and Na 2 Sn(CN 2 ) 3 crystallize in P nna ]. All structures are characterized by alternating layers of carbodiimide units and metal atoms, although cations show distinct distributions within layers. All three lithium metal carbodiimides reveal partial occupations of Li + and M 4+ on opposite sites in the order of 10 % (at room temperature). This and the general structural assembly exhibit analogies to the corresponding ternary oxides A 2 MO 3 . Furthermore, all A 2 Sn(CN 2 ) 3 structures can be related to the hierarchical NiAs type structure by space group theory via group‐subgroup relationship.
Early Detection of Alzheimer’s Disease Based on the Patient’s Creative Drawing Process: First Results with a Novel Neuropsychological Testing Method
2018-04-17

Based on the knowledge of art therapy, we developed a new neuropsychological drawing test in order to identify individuals with mild cognitive impairment (MCI) as well as dementia patients and healthy controls (HC). By observing a variety of drawing characteristics of 92 participants with a mean age of 67.7, art therapy and dementia experts discriminate HC from MCI, early dementia of the Alzheimer-type (eDAT), and moderate dementia of the Alzheimer-type (mDAT) by the process analysis of tree drawings on a digitizing tablet. The art therapist’s average categorical rating of healthy and MCI or demented individuals matched the clinical diagnosis by 88%. In a first small study, we analyzed interrater reliability, sensitivity, specificity, negative and positive predicted values of our tree drawing test (TDT) in comparison with the clock drawing test (CDT). Similar values of moderate interrater reliability were found for the TDT (0.56) as well as for the CDT (0.54). A significant high sensitivity of 0.9 within this binary impairment scale (HC versus impaired or demented) can be demonstrated. Substantial values for the specificity (0.67) could be obtained that however remain under a perfect value of the CDT (1.0). Considering 31 individuals that received the clinical diagnosis “impaired or demented” the TDT shows a higher recognition rate for the MCI group than the CDT. Furthermore in 8 of 12 borderline cases of clinical diagnosis, the outcome of the TDT diagnosis was consistent with the final clinical result.
First trimester screening for major cardiac defects based on the ductus venosus flow in fetuses with trisomy 21
2018-04-17

Abstract Objective To examine whether in fetuses with trisomy 21 (T21), the ductus venosus (DV) flow differs in presence of a major cardiac defect (congenital cardiac defect [CHD]) and whether this affects the risk distribution in first trimester screening for T21. Methods This retrospective study included pregnant women who underwent first trimester screening. This involves an examination of the crown‐rump length, the nuchal translucency, the ductus venosus (DV) flow, and the heart. Three groups of fetuses were examined: euploid without CHD, T21 with CHD, and T21 without CHD. We examined the DV pulsatility index for veins, the direction of the a‐wave, and ratios of velocities: v/S, v/D, a/S, a/D, and S/D. Results The study population consisted of 410 euploid fetuses and 136 with T21 (51 with CHD and 85 without CHD). In the 3 groups, the a‐wave was reversed in 3.2%, 66.7%, and 57.6%. The DV flow ratios in T21 with and without CDH were significantly different compared with normal fetuses. When comparing the ratios between the 2 T21 groups, only the a/S and a/D ratio were significantly different. The risk distributions in screening for T21 with and without CDH were similar. Conclusion There are some small differences in the DV flow of T21 fetuses with and without CHD, but they are not clinically useful.
Bilayer Formation vs Molecular Exchange in Organic Heterostructures: Strong Impact of Subtle Changes in Molecular Structure
2018-04-18

Organic heterostructures are a central part of a manifold of (opto)electronic devices and serve a variety of functions. Particularly, molecular monolayers on metal electrodes are of paramount importance for device performance as they allow tuning energy levels in a versatile way. However, this can be hampered by molecular exchange, i.e., by interlayer diffusion of molecules toward the metal surface. We show that the organic–metal interaction strength is the decisive factor for the arrangement in bilayers, which is the most fundamental version of organic–organic heterostructures. The subtle differences in molecular structure of 6,13-pentacenequinone (P2O) and 5,7,12,14-pentacenetetrone (P4O) lead to antithetic adsorption behavior on Ag(111): physisorption of P2O but chemisorption of P4O. This allows providing general indicators for organic–metal coupling based on shifts in photoelectron spectroscopy data and to show that the coupling strength of copper-phthalocyanine (CuPc) with Ag(111) is in between that of P2O and P4O. We find that, indeed, CuPc forms a bilayer when deposited on a monolayer P4O/Ag(111) but molecular exchange takes place with P2O, as shown by a combination of scanning tunneling microscopy and X-ray standing wave experiments.
New concepts in ANCA detection and disease classification in small vessel vasculitis: the role of ANCA antigen specificity
2018-04-18

Anti-neutrophil cytoplasmic antibodies (ANCA) play a central role in the diagnosis and pathogenesis of patients with ANCA-associated vasculitis. ANCA-associated vasculitis is a rare disease characterized by necrotizing inflammation of small/medium-sized blood vessels with and without granuloma in different organs. The main syndromes are granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic GPA. ANCA in these diseases are almost always directed against proteinase 3 and myeloperoxidase. Most laboratories worldwide use as standard the indirect immunofluorescence technique to screen for ANCA and then confirm positive IFT results with antigen specific immunoassyas for PR3- and MPO-ANCA. New guidelines for ANCA testing have been developed based on a recent European multicentre study, and according to the revised 2017 international consensus recommendations, testing for ANCA in small vessel vasculitis can be done by PR3- and MPO-ANCA immunoassays, without the categorical need for IIF. The new testing strategy for ANCA in vasculitis directly identifies the ANCA target antigen and has a particular value for the AAV sub-classification. Recent studies have shown that AAV can be classified based on ANCA serotype. ANCA presence and the antigen specificity also may have important value as a prognostic factor and may serve as a guide for immunosuppressive therapy. The clinical utility of ANCA depends on the type of assay performed and the appropiate ordering of testing the right clinical setting. Accurate identification of all patients with AAV and the avoidance of misdiagnosis can be achieved using a "gating policy" based on clinical information given to the laboratory at the time of request.
Patscanui: an intuitive web interface for searching patterns in DNA and protein data
2018-04-18

Patterns in biological sequences frequently signify interesting features in the underlying molecule. Many tools exist to search for well-known patterns. Less support is available for exploratory analysis, where no well-defined patterns are known yet. PatScanUI (https://patscan.secondarymetabolites.org/) provides a highly interactive web interface to the powerful generic pattern search tool PatScan. The complex PatScan-patterns are created in a drag-and-drop aware interface allowing researchers to do rapid prototyping of the often complicated patterns useful to identifying features of interest.
Polysialic acid is a cellular receptor for human adenovirus 52
2018-04-19

Significance We present here that adenovirus type 52 (HAdV-52) attaches to target cells through a mechanism not previously observed in other human pathogenic viruses. The interaction involves unusual, transient, electrostatic interactions between the short fiber capsid protein and polysialic acid (polySia)-containing receptors on target cells. Knowledge about the binding interactions between polySia and its natural ligands is relatively limited, and our results therefore provide additional insight not only into adenovirus biology but also into the structural basis of polySia function. Since polySia can be found in high expression levels in brain and lung cancers where its presence is associated with poor prognosis, we suggest that this polySia-binding adenovirus could be useful for design of vectors for gene therapy of these cancers.
cGMP Signaling and Vascular Smooth Muscle Cell Plasticity
2018-04-19

Cyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as atherosclerosis. Recent studies have shown that VSMCs contribute to the development of atherosclerotic plaques by clonal expansion and transdifferentiation to macrophage-like cells. VSMCs express a variety of cGMP generators and effectors, including NO-sensitive guanylyl cyclase (NO-GC) and cGMP-dependent protein kinase type I (cGKI), respectively. According to the traditional view, cGMP inhibits VSMC proliferation, but this concept has been challenged by recent findings supporting a stimulatory effect of the NO-cGMP-cGKI axis on VSMC growth. Here, we summarize the relevant studies with a focus on VSMC growth regulation by the NO-cGMP-cGKI pathway in cultured VSMCs and mouse models of atherosclerosis, restenosis, and angiogenesis. We discuss potential reasons for inconsistent results, such as the use of genetic versus pharmacological approaches and primary versus subcultured cells. We also explore how modern methods for cGMP imaging and cell tracking could help to improve our understanding of cGMP’s role in vascular plasticity. We present a revised model proposing that cGMP promotes phenotypic switching of contractile VSMCs to VSMC-derived plaque cells in atherosclerotic lesions. Regulation of vascular remodeling by cGMP is not only an interesting new therapeutic strategy, but could also result in side effects of clinically used cGMP-elevating drugs.
On the Form and Interpretation of Echo Wh-Questions
2018-04-19

We argue that echo wh-questions (EwhQs) are autonomous grammatical structures, and that their distinctive formal properties determine their semantics and pragmatics. Echo wh-sentences contain a wh-phrase in which the wh-element is narrowly focused, and a phrasal Q operator. Wh-phrase and Q operator determine a question semantics. Focus on wh determines the discourse appropriateness conditions for EwhQs, namely that an answer to the question be given in the context. A compositional analysis is provided that derives this interpretation.
Oxidation of Fe(II)–Organic Matter Complexes in the Presence of the Mixotrophic Nitrate-Reducing Fe(II)-Oxidizing Bacterium Acidovorax sp. BoFeN1
2018-04-19

Fe(II)-organic matter (Fe(II)-OM) complexes are abundant in the environment and may play a key role for the behavior of Fe and pollutants. Mixotrophic nitrate-reducing Fe(II)-oxidizing bacteria (NRFeOx) reduce nitrate coupled to the oxidation of organic compounds and Fe(II). Fe(II) oxidation may occur enzymatically or abiotically by reaction with nitrite that forms during heterotrophic denitrification. However, it is unknown whether Fe(II)-OM complexes can be oxidized by NRFeOx. We used cell-suspension experiments with the mixotrophic nitrate-reducing Fe(II)-oxidizing bacterium Acidovorax sp. strain BoFeN1 to reveal the role of nonorganically bound Fe(II) (aqueous Fe(II)) and nitrite for the rates and extent of oxidation of Fe(II)-OM complexes (Fe(II)-citrate, Fe(II)-EDTA, Fe(II)-humic acid, and Fe(II)-fulvic acid). We found that Fe(II)-OM complexation inhibited microbial nitrate-reducing Fe(II) oxidation; large colloidal and negatively charged complexes showed lower oxidation rates than aqueous Fe(II). Accumulation of nitrite and fast abiotic oxidation of Fe(II)-OM complexes only happened in the presence of aqueous Fe(II) that probably interacted with (nitrite-reducing) enzymes in the periplasm causing nitrite accumulation in the periplasm and outside of the cells, whereas Fe(II)-OM complexes probably could not enter the periplasm and cause nitrite accumulation. These results suggest that Fe(II) oxidation by mixotrophic nitrate reducers in the environment depends on Fe(II) speciation, and that aqueous Fe(II) potentially plays a critical role in regulating microbial denitrification processes.
The spatio-temporal dynamics of deviance and target detection in the passive and active auditory oddball paradigm: a sLORETA study
2018-04-19

The results provide evidence for the hypothesis that passive as well as active deviance and target detection elicit cortical activations in spatially distributed brain regions and neural networks including the ventral attention network (VAN), dorsal attention network (DAN) and salience network (SN). Based on the temporal activation of the neural sources underlying ERP modulations, a neurophysiological model of passive and active deviance and target detection is proposed which can be tested in future studies.