bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of estrogen receptor beta signaling reduces stemness of glioma stem cells
Authors: Sareddy Gangadhara R. , Pratap Uday P. , Venkata Prabhakar Pitta , Zhou Mei , Alejo Salvador , Viswanadhapalli Suryavathi , Tekmal Rajeshwar R. , Brenner Andrew J. , Vadlamudi Ratna K. 
Published: January 2021

Abstract
Glioblastoma (GBM) is the most common and deadliest tumor of the central nervous system. GBM has poor prognosis and glioma stem cells (GSCs) are implicated in tumor initiation and therapy resistance. Estrogen receptor β (ERβ) is expressed in GBM and exhibit tumor suppressive function. However, the role of ERβ in GSCs and the therapeutic potential of ERβ agonists on GSCs remain largely unknown. Here, we examined whether ERβ modulates GSCs stemness and tested the utility of two ERβ selective agonists (LY500307 and Liquiritigenin) to reduce the stemness of GSCs. The efficacy of ERβ agonists was examined on GSCs isolated from established and patient derived GBMs. Our results suggested that knockout of ERβ increased the proportion of CD133+ and SSEA+ positive GSCs and overexpression of ERβ reduced the proportion of GSCs in GBM cells. Overexpression of ERβ or treatment with ERβ agonists significantly inhibited the GSCs cell viability, neurosphere formation, self-renewal ability, induced the apoptosis and reduced expression of stemness markers in GSCs. RNA sequencing analysis revealed that ERβ agonist modulate pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that ERβ overexpression or agonist treatment reduced glutamate receptor signaling pathway and induced apoptotic pathways. In orthotopic models, ERβ overexpression or ERβ agonists treatment significantly reduced the GSCs mediated tumor growth and improved the mice overall survival. Immunohistochemical studies demonstrated that ERβ overexpression decreased SOX2 and GRM3 expression and increased expression of GFAP in tumors. These results suggest that ERβ activation could be a promising therapeutic strategy to eradicate GSCs.
Detection of Target and Suppression of Sea and Weather Clutter in Stormy Weather by Weibull/CFAR
Authors: Sayama Shuji 
Published: January 2021

AbstractIn stormy weather due to typhoon approaching the Izu Islands, I have observed sea and weather clutter containing a target (ship) using an S‐band radar with a frequency of 3.05 GHz, a beamwidth of 1.8°, a pulsewidth of 0.5 μs, and a pulse‐repetition frequency of 1600 Hz. To analyze such clutter amplitude statistics, I have used partial Q–Q plot, which is more rigorous fit of the distribution to the data than conventional Q–Q plot. It has been found that the sea and weather clutter amplitudes obey the Weibull distribution with the shape parameters of c = 6.23 for entire data and c = 5.83 to 8.78 for small data within the beamwidth of an antenna. I have applied Weibull/CFAR (constant false alarm rate) circuit configured by modifying cell‐averaging (CA) LOG/CFAR circuit to the observed data. It has been found that ship is detected, and sea and weather clutter is suppressed with improvement of 33.61 dB by Weibull/CFAR. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Pathological lesions of lambs infected in utero with bovine viral diarrhoea virus type 1c (BVDV‐1c)
Authors: Evans Caitlin A. , Woolford Lucy , Hemmatzadeh Farhid , Reichel Michael P. , Cockcroft Peter D. 
Published: January 2021

AbstractBackground: Acute bovine viral diarrhoea virus (BVDV) infections in sheep are largely sub‐clinical although infections of pregnant ewes have shown to result in significant fetal losses and persistently infected lambs. However, the extent and severity of abnormalities in lambs infected with BVDV in utero is still largely unknown.Methods: Twenty‐two ewes were experimentally infected with BVDV‐1c between 59 and 69 days of gestation. Fifteen lambs were submitted for pathological examination and the abnormalities observed in lambs and fetuses characterised.Results: Six lambs were identified as BVDV negative, and nine were identified as BVDV positive. Anasarca and cholestatic hepatopathy was observed in four BVDV positive lambs and associated with ewes with early seroconversion. One BVDV positive lamb was born with muscular tremors and a hairy coat associated with primary follicular dysplasia, a developmental abnormality normally associated with border disease infected lambs.Conclusion: If similar lambing outcomes are identified in a commercial setting then BVDV should be considered, particularly in areas where sheep regularly come in to contact with cattle. In addition, as far as the authors are aware, this is the first reported case of a ‘hairy shaker’ lamb born as a result of an infection with BVDV‐1c in Australia.
Revision rate of THA in patients younger than 40 years depends on primary diagnosis – a retrospective analysis with a minimum follow-up of 10 years
Authors: Rahm Stefan , Hoch Armando , Tondelli Timo , Fuchs Johannes , Zingg Patrick O. 
Published: January 2021

Abstract
Background
Treating osteoarthritis in elderly patients with THA is very successful. However, surgeons hesitate to recommend THA in younger patients. The spectrum of etiologies for end stage hip disease in the younger population is diverse and therefore different courses may be assumed. Our objective was to evaluate THA revision rate within a minimum follow-up period of 10 years in young patients and to analyze the difference between different primary diagnoses.

Methods
We included 144 consecutive hips in 127 patients younger than 40 years, who received a primary THA from 01/1996 to 12/2007. Operative reports, clinical and radiographic documentation were reviewed to determine primary diagnosis, prior hip surgery, component specifications and revision surgery. 111 hips in 97 patients were available for outcome analysis with a minimum follow-up of 10 years.

Results
The mean age was 33 years (range 15–40 years) at the time of the index THA, 68 patients were female and 59 were male. Ten years revision rate on the prosthetic components was 13%. The most common primary diagnosis was DDH. DDH was associated with a risk of 17% for requiring a reoperation on the prosthetic components because of mechanical fatigue and therefore, significantly higher than for any other primary diagnosis (p = 0.005).

Conclusion
THA in young patients is associated with a high revision rate of 13% in 10 years. 17% of patients with DDH required revision surgery for mechanical fatigue within 10 years, which was significantly higher than for any other primary diagnosis (1.2%, OR 16.8).
Multi-Frequency and Single-Crystal EPR on V4+ in W-Doped β-Vanadyl(V) Phosphate: Hyperfine Coupling- and g-Tensor Values and Orientation
Authors: NejatyJahromy Yaser , Roy Subrata Chandra , Glaum Robert , Schiemann Olav 
Published: January 2021

AbstractDifferent structure types of vanadyl(V) orthophosphate [i.e. (VV ≡O)3+ orthophosphate] have been subjects of research due to their catalytic activity in the oxidation of n-butane to maleic anhydride. Electron paramagnetic resonance (EPR) spectroscopy can be exploited to elucidate the electronic structure of such compounds. When tuning the oxidation state of vanadium in (V1-xWx)OPO4, X-band EPR spectra have confirmed the presence of paramagnetic V4+ ions. However, some of the features in these spectra could not be explained. Here, powder samples of β-(VIV0.01VV.98WVI.01)OPO4 are investigated at S-, X- and Q- band, along with X-band EPR measurements on single crystals. Thereby, the discrepancies between the spectra and their simulations could be resolved. In particular, it could be shown that the g and A tensors are not coaxial. The resulting consistent EPR picture and the refined paramagnetic parameters are reported. The work underlines the indispensability of a multi-frequency approach in EPR for unequivocal conclusions.
Using Interleaved Stimulation to Measure the Size and Selectivity of the Sustained Phase-Locked Neural Response to Cochlear Implant Stimulation
Authors: Carlyon Robert P. , Guérit François , Deeks John M. , Harland Andrew , Gransier Robin , Wouters Jan , de Rijk Simone R. , Bance Manohar 
Published: January 2021

AbstractWe measured the sustained neural response to electrical stimulation by a cochlear implant (CI). To do so, we interleaved two stimuli with frequencies F1 and F2 Hz and recorded a neural distortion response (NDR) at F2-F1 Hz. We show that, because any one time point contains only the F1 or F2 stimulus, the instantaneous nonlinearities typical of electrical artefact should not produce distortion at this frequency. However, if the stimulus is smoothed, such as by charge integration at the nerve membrane, subsequent (neural) nonlinearities can produce a component at F2-F1 Hz. We stimulated a single CI electrode with interleaved sinusoids or interleaved amplitude-modulated pulse trains such that F2 = 1.5F1, and found no evidence for an NDR when F2-F1 was between 90 and 120 Hz. However, interleaved amplitude-modulated pulse trains with F2-F1~40 Hz revealed a substantial NDR with a group delay of about 45 ms, consistent with a thalamic and/or cortical response. The NDR could be measured even from recording electrodes adjacent to the implant and at the highest pulse rates (> 4000 pps) used clinically. We then measured the selectivity of this sustained response by presenting F1 and F2 to different electrodes and at different between-electrode distances. This revealed a broad tuning that, we argue, reflects the overlap between the excitation elicited by the two electrodes. Our results also provide a glimpse of the neural nonlinearity in the auditory system, unaffected by the biomechanical cochlear nonlinearities that accompany acoustic stimulation. Several potential clinical applications of our findings are discussed.
Enabling scalable and fault-tolerant multi-agent systems by utilizing cloud-native computing
Authors: Dähling Stefan , Razik Lukas , Monti Antonello 
Published: January 2021

AbstractMulti-agent systems (MAS) represent a distributed computing paradigm well suited to tackle today’s challenges in the field of the Internet of Things (IoT). Both share many similarities such as the interconnection of distributed devices and their cooperation. The combination of MAS and IoT would allow the transfer of the experience gained in MAS research to the broader range of IoT applications. The key enabler for utilizing MAS in the IoT is the ability to build large-scale and fault-tolerant MASs since IoT concepts comprise possibly thousands or even millions of devices. However, well known multi-agent platforms (MAP), e. g., Java Agent DE-velopment Framework (JADE), are not able to deal with these challenges. To this aim, we present a cloud-native Multi-Agent Platform (cloneMAP) as a modern MAP based on cloud-computing techniques to enable scalability and fault-tolerance. A microservice architecture is used to implement it in a distributed way utilizing the open-source container orchestration system Kubernetes. Thereby, bottlenecks and single-points of failure are conceptually avoided. A comparison with JADE via relevant performance metrics indicates the massively improved scalability. Furthermore, the implementation of a large-scale use case verifies cloneMAP’s suitability for IoT applications. This leads to the conclusion that cloneMAP extends the range of possible MAS applications and enables the integration with IoT concepts.
Exploring the role of lexis and grammar for the stable identification of register in an unrestricted corpus of web documents
Authors: Laippala Veronika , Egbert Jesse , Biber Douglas , Kyröläinen Aki-Juhani 
Published: January 2021

AbstractThe Internet offers great possibilities for many scientific disciplines that utilize text data. However, the potential of online data can be limited by the lack of information on the genre or register of the documents, as register—whether a text is, e.g., a news article or a recipe—is arguably the most important predictor of linguistic variation (see Biber in Corpus Linguist Linguist Theory 8:9–37, 2012). Despite having received significant attention in recent years, the modeling of online registers has faced a number of challenges, and previous studies have presented contradictory results. In particular, these have concerned (1) the extent to which registers can be automatically identified in a large, unrestricted corpus of web documents and (2) the stability of the models, specifically the kinds of linguistic features that achieve the best performance while reflecting the registers instead of corpus idiosyncrasies. Furthermore, although the linguistic properties of registers vary importantly in a number of ways that may affect their modeling, this variation is often bypassed. In this article, we tackle these issues. We model online registers in the largest available corpus of online registers, the Corpus of Online Registers of English (CORE). Additionally, we evaluate the stability of the models towards corpus idiosyncrasies, analyze the role of different linguistic features in them, and examine how individual registers differ in these two aspects. We show that (1) competitive classification performance on a large-scale, unrestricted corpus can be achieved through a combination of lexico-grammatical features, (2) the inclusion of grammatical information improves the stability of the model, whereas many of the previously best-performing feature sets are less stable, and that (3) registers can be placed in a continuum based on the discriminative importance of lexis and grammar. These register-specific characteristics can explain the variation observed in previous studies concerning the automatic identification of online registers and the importance of different linguistic features for them. Thus, our results offer explanations for the jungle-likeness of online data and provide essential information on online registers for all studies using online data.
Finding multi-objective supported efficient spanning trees
Authors: Correia Pedro , Paquete Luís , Figueira José Rui 
Published: January 2021

AbstractThis article introduces a new algorithm for computing the set of supported non-dominated points in the objective space and all the corresponding efficient solutions in the decision space for the multi-objective spanning tree (MOST) problem. This algorithm is based on the connectedness property of the set of efficient supported solutions and uses a decomposition of the weight set in the weighting space defined for a parametric version of the MOST problem. This decomposition is performed through a space reduction approach until an indifference region for each supported non-dominated point is obtained. An adjacency relation defined in the decision space is used to compute all the supported efficient spanning trees associated to the same non-dominated supported point as well as to define the indifference region of the next points. An in-depth computational analysis of this approach for different types of networks with three objectives is also presented.
ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update)
Authors: Hoffmann Michael B. , Bach Michael , Kondo Mineo , Li Shiying , Walker Sinead , Holopigian Karen , Viswanathan Suresh , Robson Anthony G. 
Published: January 2021

AbstractThe multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV standard for clinical mfERG and defines minimum protocols for basic clinical mfERG recording and reporting so that responses can be recognized and compared from different laboratories worldwide. The major changes compared with the previous mfERG standard relate to the minimum length of m-sequences used for recording, reporting of results and a change in document format, to be more consistent with other ISCEV standards.
A novel ligand of the translationally controlled tumor protein (TCTP) identified by virtual drug screening for cancer differentiation therapy
Authors: Fischer Nicolas , Seo Ean-Jeong , Abdelfatah Sara , Fleischer Edmond , Klinger Anette , Efferth Thomas 
Published: January 2021

SummaryIntroduction Differentiation therapy is a promising strategy for cancer treatment. The translationally controlled tumor protein (TCTP) is an encouraging target in this context. By now, this field of research is still at its infancy, which motivated us to perform a large-scale screening for the identification of novel ligands of TCTP. We studied the binding mode and the effect of TCTP blockade on the cell cycle in different cancer cell lines. Methods Based on the ZINC-database, we performed virtual screening of 2,556,750 compounds to analyze the binding of small molecules to TCTP. The in silico results were confirmed by microscale thermophoresis. The effect of the new ligand molecules was investigated on cancer cell survival, flow cytometric cell cycle analysis and protein expression by Western blotting and co-immunoprecipitation in MOLT-4, MDA-MB-231, SK-OV-3 and MCF-7 cells. Results Large-scale virtual screening by PyRx combined with molecular docking by AutoDock4 revealed five candidate compounds. By microscale thermophoresis, ZINC10157406 (6-(4-fluorophenyl)-2-[(8-methoxy-4-methyl-2-quinazolinyl)amino]-4(3H)-pyrimidinone) was identified as TCTP ligand with a KD of 0.87 ± 0.38. ZINC10157406 revealed growth inhibitory effects and caused G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. ZINC10157406 (2 × IC50) downregulated TCTP expression by 86.70 ± 0.44% and upregulated p53 expression by 177.60 ± 12.46%. We validated ZINC10157406 binding to the p53 interaction site of TCTP and replacing p53 by co-immunoprecipitation. Discussion ZINC10157406 was identified as potent ligand of TCTP by in silico and in vitro methods. The compound bound to TCTP with a considerably higher affinity compared to artesunate as known TCTP inhibitor. We were able to demonstrate the effect of TCTP blockade at the p53 binding site, i.e. expression of TCTP decreased, whereas p53 expression increased. This effect was accompanied by a dose-dependent decrease of CDK2, CDK4, CDK, cyclin D1 and cyclin D3 causing a G0/G1 cell cycle arrest in MOLT-4, SK-OV-3 and MCF-7 cells. Our findings are supposed to stimulate further research on TCTP-specific small molecules for differentiation therapy in oncology.
Commentary on a special issue: Davydov’s approach in the XXI century
Authors: Coles Alf 
Published: January 2021

AbstractThe articles in this special issue, collectively, provide overwhelming evidence that a curriculum which has as its primary basis the counting of discrete objects (and hence which introduces numbers as discrete) is not an effective or rational organisation. In this commentary, I discuss the contribution of each article to an understanding of Davydov’s ontology and epistemology, issues around the transposition of a pedagogy or curriculum from one country to another, early algebra and proportional or multiplicative reasoning. From Davydov’s own research and the writing in these articles, we know children are able to understand abstract structures from an early age. The thinking in this special issue provides tools to investigate and question any context in which such understanding is not routinely taking hold.
A PITX2 splice-site mutation in a family with Axenfeld-Rieger syndrome leads to decreased expression of nuclear PITX2 protein
Authors: Zhang Feng , Zhang Lusi , He Li , Cao Mengdan , Yang Yuting , Duan Xuanchu , Shi Jingming , Liu Ke 
Published: January 2021

Abstract
Purpose
Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder characterized by ocular anterior segment abnormalities. In the current study, we describe clinical and genetic findings in a Chinese ARS pedigree.

Methods
An ARS pedigree was recruited and patients were given comprehensive ophthalmic examinations and general physical examinations. DNA from the proband II:2 was used for exome sequencing. Sanger sequencing was utilized to identify and validate PITX2 variations. qPCR and western blotting were performed to detect PITX2 expression in immortalized peripheral blood lymphocytes.

Results
All affected family members showed typical ocular abnormalities, including iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. They also exhibited systemic anomalies, such as microdontia, hypodontia, and redundant periumbilical skin. A heterozygous splice-site variation c.390 + 1G > A in PITX2, which might lead to a truncated PITX2 protein (p.Val131IlefsX127), was found in the proband. Sanger sequencing validated that the variation completely co-segregated with the ARS phenotype within this family and was absent in 100 unrelated controls. Western blotting revealed that the nuclear PITX2 protein was significantly decreased in patients compared with controls. Nonetheless, there was no significant difference in the total PITX2 protein level, consistent with qPCR results showing no alteration in PITX2 mRNA levels in the patient group.

Conclusions
PITX2 c.390 + 1G > A (p.Val131IlefsX127) was a novel genetic etiology of the ARS pedigree. The mutation leads to decreased nuclear PITX2, indicating lower transcriptional activity.
Two-step synthesis of niobium doped Na–Ca–(Mg)–P–Si–O glasses
Authors: Wójcik N. A. , Ali S. , Mielewczyk-Gryń A. , Jonson B. 
Published: January 2021

AbstractNiobium doped biosolubility glasses in the Na–Ca–(Mg)–P–Si–O system were prepared by using an untypical two-step synthesis route. The parent glass was melted in air atmosphere at 1350 °C followed by re-melting the glass in Nb crucible with the addition of metallic Mg/Ca powder in the nitrogen atmosphere. The second melting step was carried out at 1450–1650 °C, using an induction furnace. The topography and structure of the obtained glasses were characterized by confocal microscopy, X-ray powder diffraction and infrared spectroscopic techniques. The chemical compositions were examined by energy-dispersive X-ray spectroscopy (EDS). The glasses were found to be of grayish color, X-ray amorphous and having network connectivity between ~ 2.5 and 2.7. The network connectivity of re-melted glasses was lower than the one of the parent glass. The glass structure consists of a highly disrupted silicate network of predominantly Q2 groups as well as isolated orthophosphate tetrahedra. The parent glass contains nanocrystallites consisted of apatitic PO43− groups. The re-melted glasses contain non-apatitic or amorphous calcium phosphates. The obtained glass transition temperatures range from 530 to 568 °C and exhibit higher values for glassed doped with Ca metal. These glasses have improved thermal stability as compared to reference bioglasses. The biosolubility test in phosphate buffered saline solution (PBS) confirms that the glasses have biosolubility properties and HAp formation on the surfaces was observed.