julilili42/papers huggingface dataset:
Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL‑1β and the SGK1‑NFAT2 signaling pathway
2020-04-24

Bladder outlet obstruction (BOO), which is primarily caused by benign prostatic hyperplasia, is a common chronic disease. However, previous studies have most commonly investigated BOO using the acute obstruction model. In the present study, a chronic obstruction model was established to investigate the different pathological alterations in the bladder between acute and chronic obstruction. Compared with chronic obstruction, acute obstruction led to increased expression of proliferating cell nuclear antigen and interleukin‐1β, which are markers of proliferation and inflammation, respectively. Furthermore, increased fibrosis in the bladder at week 2 was observed. Low pressure promoted mice bladder smooth muscle cell (MBSMC) proliferation, and pressure overload inhibited cell proliferation and increased the proportion of dead MBSMCs. Further investigation using serum/glucocorticoid regulated kinase 1 (SGK1) small interfering RNAs indicated that low pressure may promote MBSMC proliferation by upregulating SGK1 and nuclear factor of activated T‐cell expression levels. Therefore, the present study suggested that acute obstruction led to faster decompensation of bladder function and chronic bladder obstruction displayed an enhanced ability to progress to BOO.
Nanoscale Organolanthanum Clusters: Nuclearity‐Directing Role of Cyclopentadienyl and Halogenido Ligands
2020-04-24

Abstract Tetramethylaluminato/halogenido(X) ligand exchange reactions in half‐sandwich complexes [Cp R La(AlMe 4 ) 2 ] are feasible in non‐coordinating solvents and provide access to large coordination clusters of the type [Cp R LaX 2 ] x . Incomplete exchange reactions generate the hexalanthanum clusters [Cp R 6 La 6 X 8 (AlMe 4 ) 4 ] (Cp R =Cp*=C 5 Me 5 , X=I; Cp R =Cp′=C 5 H 4 SiMe 3 , X=Br, I). Treatment of [Cp*La(AlMe 4 ) 2 ] with two equivalents Me 3 SiI gave the nonalanthanum cluster [Cp*LaI 2 ] 9 , while the exhaustive reaction of [Cp′La(AlMe 4 ) 2 ] with the halogenido transfer reagents Me 3 GeX and Me 3 SiX (X=I, Br, Cl) produced a series of monocyclopentadienyl rare‐earth‐metal clusters with distinct nuclearity. Depending on the halogenido ion size the homometallic clusters [Cp′LaCl 2 ] 10 and [Cp′LaX 2 ] 12 (X=Br, I) could be isolated, whereas different crystallization techniques led to the aggregation of clusters of distinct structural motifs, including the desilylated cyclopentadienyl‐bridged cluster [(μ‐Cp) 2 Cp′ 8 La 8 I 14 ] and the heteroaluminato derivative [Cp′ 10 La 10 Br 18 (AlBr 2 Me 2 ) 2 ]. The use of the Cp′ ancillary ligand facilitates cluster characterization by means of NMR spectroscopy.
Ordered Donor–Acceptor Complex Formation and Electron Transfer in Co-deposited Films of Structurally Dissimilar Molecules
2020-04-24

The electrical and optoelectronic properties of organic semiconductor thin films can be tailored by mixing two molecular materials, e.g., by co-deposition. Possible resulting morphologies include phase separation or mixed crystals, which can form either solid solutions or ordered complexes, but it is difficult to predict a priori the morphology that will result for a given material combination. Here, we study electron transfer between planar electron-donor molecules and a nonplanar electron acceptor in co-deposited films by analyzing morphological, vibrational, and optical properties. For the donor under study here that does not undergo ground-state electron transfer to the acceptor, we find phase separation in mixed film. If ground-state electron transfer is present, the balance between crystal binding energy of the single-component materials and the Coulomb attraction between ions formed in the co-deposited film drives the co-deposited films either into phase separation or mixed-crystal formation. To rationalize the resulting morphology of these co-deposited films within the laws of thermodynamics, it is necessary to consider structural incompatibility of the molecules as well as the Coulomb attraction between molecular ions when formed via ground-state electron transfer.
Obituary for Tamara Grummt
2020-04-24

Abstract Tamara Grummt passed away on January 26, 2020 in Oelsnitz/Vogtland, Germany. Tamara was one of the scientific pioneers in the field of environmental toxicology, namely genotoxicity and hygiene of drinking and bathing waters. Her passing is not only a great loss to environmental research and to the global environmental toxicology community—we have lost an outstanding personality with the heart in the right place, who has become, for many of us, a wonderful friend.
Open Software/Hardware Platform for Human-Computer Interface Based on Electrooculography (EOG) Signal Classification
2020-04-25

Electrooculography (EOG) signals have been widely used in Human-Computer Interfaces (HCI). The HCI systems proposed in the literature make use of self-designed or closed environments, which restrict the number of potential users and applications. Here, we present a system for classifying four directions of eye movements employing EOG signals. The system is based on open source ecosystems, the Raspberry Pi single-board computer, the OpenBCI biosignal acquisition device, and an open-source python library. The designed system provides a cheap, compact, and easy to carry system that can be replicated or modified. We used Maximum, Minimum, and Median trial values as features to create a Support Vector Machine (SVM) classifier. A mean of 90% accuracy was obtained from 7 out of 10 subjects for online classification of Up, Down, Left, and Right movements. This classification system can be used as an input for an HCI, i.e., for assisted communication in paralyzed people.
Chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes
2020-04-25

Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes enabling separation of the whole-genome sequencing reads into haplotype-specific reads sets. After assembling the reads of each haplotype, the contigs are scaffolded to chromosome-level using a genetic map derived from the gametes. As a proof-of-concept, we assembled the two genomes of a diploid apricot tree based on whole-genome sequencing of 445 individual pollen grains. The two haplotype assemblies (N50: 25.5 and 25.8 Mb) featured a haplotyping precision of &gt;99% and were accurately scaffolded to chromosome-level.
Inducible expression of (pp)pGpp synthetases inStaphylococcus aureusis associated with activation of stress response genes
2020-04-25

Abstract The stringent response is characterized by the synthesis of the messenger molecules pppGpp, ppGpp or pGpp (here collectively designated (pp)pGpp). The phenotypic consequences resulting from (pp)pGpp accumulation vary among species and can be mediated by different underlying mechanisms. Most genome-wide analyses have been performed under stress conditions, which often mask the immediate effects of (pp)pGpp-mediated regulatory circuits. In Staphylococcus aureus , (pp)pGpp can be synthesized via the RelA-SpoT-homolog (RSH Sau ) upon amino acid limitation or via one of the two small (pp)pGpp synthetases RelP or RelQ, upon cell wall stress. We used RNA-Seq to compare the global effects in response to transcriptional induction of the synthetase domain of RSH (RSH-Syn), RelP or RelQ without the need to apply additional stress conditions. Enzyme expression resulted in changes in the nucleotide pool similar to induction of the stringent response via the tRNA synthetase inhibitor mupirocin: a reduction in the GTP pool, an increase in the ATP pool and synthesis of pppGpp, ppGpp and pGpp. Induction of all three enzymes resulted in similar changes in the transcriptome. However, RelQ was less active than RSH-Syn and RelP, indicating strong restriction of its (pp)pGpp-synthesis activity in vivo . Genes involved in the SOS response, iron storage (e.g. ftnA, dps ), oxidative stress response (e.g., katA, sodA ) and the the psmα1-4 and psmß1-2 operons coding for cytotoxic, phenole soluble modulins (PSMs) were highly upregulated upon (pp)pGpp synthesis. Analyses of the ftnA, dps and psm genes in different regulatory mutants revealed that their (pp)pGpp-dependent regulation can occur independent of the regulators PerR, Fur, SarA or CodY. Moreover, psm expression is uncoupled from expression of the quorum sensing system Agr, the main known psm activator. The expression of central genes of the oxidative stress response protects the bacteria from anticipated ROS stress derived from PSMs or exogenous sources. Thus, we identified a new link between the stringent response and oxidative stress in S. aureus that is likely crucial for survival upon phagocytosis. Significance Most bacteria make use of the second messenger (pp)pGpp to reprogram bacterial metabolism under nutrient-limiting conditions. In the human pathogen Staphylococcus aureus , (pp)pGpp plays an important role in virulence, phagosomal escape and antibiotic tolerance. Here, we analyzed the immediate consequences of (pp)pGpp synthesis upon transcriptional induction of the (pp)pGpp-producing enzymes RSH, RelP or RelQ. (pp)pGpp synthesis provokes immediate changes in the nucleotide pool and severely impacts the expression of hundreds of genes. A main consequence of (pp)pGpp synthesis in S. aureus is the induction of ROS-inducing toxic phenol-soluble modulins (PSMs) and simultaneous expression of the detoxifying system to protect the producer. This mechanism is likely of special advantage for the pathogen after phagocytosis.
Succinct dynamic variation graphs
2020-04-25

Abstract Motivation Pangenomics is a growing field within computational genomics. Many pangenomic analyses use bidirected sequence graphs as their core data model. However, implementing and correctly using this data model can be difficult, and the scale of pangenomic data sets can be challenging to work at. These challenges have impeded progress in this field. Results Here we present a stack of two C++ libraries, libbdsg and libhandlegraph , which use a simple, field-proven interface, designed to expose elementary features of these graphs while preventing common graph manipulation mistakes. The libraries also provide a Python binding. Using a diverse collection of pangenome graphs, we demonstrate that these tools allow for efficient construction and manipulation of large genome graphs with dense variation. For instance, the speed and memory usage is up to an order of magnitude better than the prior graph implementation in the vg toolkit, which has now transitioned to using libbdsg ’s implementations. Availability libhandlegraph and libbdsg are available under an MIT License from https://github.com/vgteam/libhandlegraph and https://github.com/vgteam/libbdsg . Contact erik.garrison@ucsc.edu
Atmospheric and Oceanographic Signatures in the Ice Shelf Channel Morphology of Roi Baudouin Ice Shelf, East Antarctica, Inferred From Radar Data
2020-04-26

Ice shelves around Antarctica can provide back stress for outlet glaciers and control ice sheet mass loss. They often contain narrow bands of thin ice termed ice shelf channels. Ice shelf channel morphology can be interpreted through surface depressions and exhibits junctions and deflections from flowlines. Using ice flow modeling and radar, we investigate ice shelf channels in the Roi Baudouin Ice Shelf. These are aligned obliquely to the prevailing easterly winds. In the shallow radar stratigraphy, syncline and anticline stacks occur beneath the upwind and downwind side, respectively. The structures are horizontally and vertically coherent, except near an ice shelf channel junction where patterns change structurally with depth. Deeper layers truncate near basal incisions. Using ice flow modeling, we show that the stratigraphy is ∼9 times more sensitive to atmospheric variability than to oceanic variability. This is due to the continual adjustment toward flotation. We propose that syncline‐anticline pairs in the shallow stratigraphy are caused by preferential snow deposition on the windward side and wind erosion at the downwind side. This drives downwind deflection of ice shelf channels of several meters per year. The depth variable structures indicate formation of an ice shelf channel junction by basal melting. We conclude that many ice shelf channels are seeded at the grounding line. Their morphology farther seaward is shaped on different length scales by ice dynamics, the ocean, and the atmosphere. These processes act on finer (subkilometer) scales than are captured by most ice, atmosphere, and ocean models, yet the dynamics of ice shelf channels may have broader implications for ice shelf stability.
Enhanced Serum Levels of sFlt1: Impact on Materno–Fetal CMV Transmission
2020-04-26

Background: Antenatal Cytomegalovirus infection (CMV) can be associated with severe fetal symptoms and newborn outcome. The current prenatal diagnosis is based on amniocentesis (AC). No reliable biomarker for fetal infection is available. Methods: We measured Placenta-derived growth factor (PlGF), and soluble fms-like tyrosine kinase 1 (sFlt1), concentrations in maternal serum and amniotic fluid (AF) in context of maternal CMV primary infection. Blood sampling was carried out at the time of AC for detection of fetal CMV infection. The study cohort was divided into four subcohorts according to the presence or absence of fetal infection and preemptive hyperimmunoglobulin (HIG) treatment during the time interval between diagnosis of the CMV primary infection and AC. Results: The study cohort involved 114 pregnancies. In the non-transmitting subcohorts (NT) with and without prior HIG treatment, the median sFlt1 concentrations were 1.5 ng/mL (NT, HIG+) and 1.4 ng/mL (NT, HIG−), respectively. In the two transmitting groups (T) the concentrations were 1.3 ng/mL (T, HIG+) and 2.3 ng/mL (T, HIG−), respectively (NT, HIG− vs. T, HIG−, p &lt; 0.001). The corresponding PlGF levels and the sFlt1/PlGF ratios showed no significant differences between the cohorts. The empirical cut-off values &lt;1504 pg/mL sFlt1 and &lt;307 pg/mL PlGF, were associated with the exclusion of CMV transmission (p &lt; 0.001). Conclusion: sFlt1 concentration in the maternal blood could be a predictive biomarker for maternofetal CMV transmission.
Meta Research: Replication of Significant Results --- Modeling the Effects of p-Hacking
2020-04-26

This article examines why many studies fail to replicate statistically significant published results. We address this issue within a general statistical framework that also allows usto include various questionable research practices that are thought to reduce replicability. The analyses indicate that the base rate of true effects is the major factor that determines the replication rate of scientific results. Specifically, for purely statistical reasons, replicability is low in research domains where true effects are rare (e.g., search for effective drugs in pharmacology). This point is under-appreciated in current scientific and media discussions of replicability.
Clinico‐Genetic, Imaging and Molecular Delineation of COQ8A‐Ataxia: A Multicenter Study of 59 Patients
2020-04-27

Objective To foster trial‐readiness of coenzyme Q8A (COQ8A)‐ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A‐ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). Methods Cross‐modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype–phenotype correlations, 3D‐protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. Results Fifty‐nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A‐ataxia presented as variable multisystemic, early‐onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss‐of‐function variants (82–93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross‐sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild‐to‐moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: −0.81/year). Explorative sample size calculations indicate that ≥48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. Interpretation This study provides a deeper understanding of the disease, and paves the way toward large‐scale natural history studies and treatment trials in COQ8A‐ataxia. ANN NEUROL 2020;88:251–263
In situ airborne measurements of atmospheric and sea surface parameters related to offshore wind parks in the German Bight
2020-04-27

Abstract. Between 6 September 2016 and 15 October 2017, meteorological measurement flights were conducted above the German Bight in the framework of the project WIPAFF (Wind Park Far Field). The scope of the measurements was to study long-range wakes with an extent larger than 10 km behind entire wind parks, and to investigate the interaction of wind parks and the marine atmospheric boundary layer. The research aircraft Dornier 128 of the Technische Universität (TU) Braunschweig performed in total 41 measurement flights during different seasons and different stability conditions. The instrumentation consisted of a nose boom with sensors for measuring the wind vector, temperature and humidity, and additionally sensors for characterizing the water surface, a surface temperature sensor, a laser scanner and two cameras in the visible and infrared wavelength range. A detailed overview of the aircraft, sensors, data post-processing and flight patterns is provided here. Further, averaged profiles of atmospheric parameters illustrate the range of conditions. The potential use of the data set has been shown already by first publications. The data are publicly available in the world data centre PANGAEA (https://doi.org/10.1594/PANGAEA.902845; Bärfuss et al., 2019a).
Intraindividual Neurofilament Dynamics in Serum Mark the Conversion to Sporadic Parkinson's Disease
2020-04-27

Abstract Background and Objectives With disease‐modifying treatment strategies on the horizon, stratification of individual patients at the earliest stages of Parkinson's disease (PD) is key—ideally already at clinical disease onset. Blood levels of neurofilament light chain (NfL) provide an easily accessible fluid biomarker that might allow capturing the conversion from prodromal to manifest PD. Methods We assessed longitudinal serum NfL levels in subjects converting from prodromal to manifest sporadic PD (converters), at‐risk subjects, and matched controls (72 participants with ≈4 visits), using single‐molecule array (Simoa) technique. Results While NfL levels were not increased at the prodromal stage, subjects converting to the manifest motor stage showed a significant intraindividual acceleration of the age‐dependent increase of NfL levels. Conclusions The temporal dynamics of intraindividual NfL blood levels might mark the conversion to clinically manifest PD, providing a potential stratification biomarker for individual disease onset in the advent of precision medicine for PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Phase III randomized, double‐blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum‐containing regimen (RADPAC)
2020-04-27

Abstract The RADPAC trial evaluated paclitaxel with everolimus in patients with advanced gastroesophageal cancer (GEC) who have progressed after therapy with a fluoropyrimidine/platinum‐containing regimen. Patients were randomly assigned to receive paclitaxel (80 mg/m 2 ) on day 1, 8 and 15 plus everolimus (10 mg daily, arm B) d1‐d28 or placebo (arm A), repeated every 28 days. Primary end point was overall survival (OS). Efficacy was assessed in the intention‐to‐treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov , number NCT01248403. Between October 2011 and September 2015, 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (arm A, 150, arm B, 150). In the intention to treat population, there was no significant difference in progression‐free survival (PFS; everolimus, 2.2 vs placebo, 2.07 months, HR 0.88, P = .3) or OS (everolimus, 6.1 vs placebo, 5.0 months, HR 0.93, P = .54). For patients with prior taxane use, everolimus improved PFS (everolimus, 2.7 vs placebo 1.8 months, HR 0.69, P = .03) and OS (everolimus, 5.8 vs placebo 3.9 months, HR 0.73, P = .07). Combination of paclitaxel and everolimus was associated with significantly more grade 3‐5 mucositis (13.3% vs 0.7%; P &lt; .001). The addition of everolimus to paclitaxel did not improve outcomes in pretreated metastatic gastric/gastroesophageal junction (GEJ) cancer. Activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit.
Multiwavelength observations of PSR J2032+4127 during the 2017 periastron passage
2020-04-27

ABSTRACT PSR J2032+4127 is only the second known gamma-ray binary where it is confirmed that a young radio pulsar is in orbit around a Be-star. The interaction of the pulsar wind with the mass outflow from the companion leads to broad-band emission from radio up to TeV energies. In this paper we present results of optical monitoring of the 2017 periastron passage with the Nordic Optical Telescope. These observations are complemented by X-ray (Swift/XRT, NuSTAR) and GeV (Fermi/LAT) monitoring. Joint analysis of the evolution of the parameters of the H α line and the broad-band (X-ray to TeV) spectral shape allows us to propose a model linking the observed emission to the interaction of the pulsar and Be-star winds under the assumption of the inclined disc geometry. Our model allows the observed flux and spectral evolution of the system to be explained in a self-consistent way.
A New Modification of TeI4 Possessing the Crystal Structure Proposed for WI4
2020-04-27

A modification of TeI4 (ζ-TeI4) was discovered in an attempt to reproduce a reported synthesis of WI4, beginning from WTe2 and iodine. The crystal structure of ζ-TeI4 was solved from single-crystal data in the triclinic space group P1, isotypic with the structure of the previously reported WI4. The crystal structure of ζ-TeI4 contains isolated tetrameric Te4I16 molecules, in which tellurium atoms are coordinated by six iodine atoms. Electron microprobe and ICP-OES measurements confirm the identity of the new phase and make the formation of WI4 via this synthesis route implausible. A comparison of ζ-TeI4 with all other TeI4 polymorphs is drawn by DFT calculations and structural relationships. Special conditions regarding the formation of ζ-TeI4 as well as the phase transition from δ-TeI4 into ζ-TeI4 are reported.