bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dual Reporter EndoC-βH1 Human β-Cell Line for Efficient Quantification of Calcium Flux and Insulin Secretion
Authors: Cardenas-Diaz Fabian L , Leavens Karla F , Kishore Siddharth , Osorio-Quintero Catherine , Chen Yi-Ju , Stanger Ben Z , Wang Pei , French Deborah , Gadue Paul 
Published: January 2020

Abstract
Human in vitro model systems of diabetes are critical to both study disease pathophysiology and offer a platform for drug testing. We have generated a set of tools in the human β-cell line EndoC-βH1 that allows the efficient and inexpensive characterization of β-cell physiology and phenotypes driven by disruption of candidate genes. First, we generated a dual reporter line that expresses a preproinsulin–luciferase fusion protein along with GCaMP6s. This reporter line allows the quantification of insulin secretion by measuring luciferase activity and calcium flux, a critical signaling step required for insulin secretion, via fluorescence microscopy. Using these tools, we demonstrate that the generation of the reporter human β-cell line was highly efficient and validated that luciferase activity could accurately reflect insulin secretion. Second, we used a lentiviral vector carrying the CRISPR-Cas9 system to generate candidate gene disruptions in the reporter line. We also show that we can achieve gene disruption in ~90% of cells using a CRISPR–Cas9 lentiviral system. As a proof of principle, we disrupt the β-cell master regulator, PDX1, and show that mutant EndoC-βH1 cells display impaired calcium responses and fail to secrete insulin when stimulated with high glucose. Furthermore, we show that PDX1 mutant EndoC-βH1 cells exhibit decreased expression of the β-cell-specific genes MAFA and NKX6.1 and increased GCG expression. The system presented here provides a platform to quickly and easily test β-cell functionality in wildtype and cells lacking a gene of interest.
Non-canonical regulation of homologous recombination DNA repair by the USP9X deubiquitylase
Authors: O'Dea Rachel , Santocanale Corrado 
Published: January 2020

ABSTRACT
In order to prevent the deleterious effects of genotoxic agents, cells have developed complex surveillance mechanisms and DNA repair pathways that allow them to maintain genome integrity. The ubiquitin-specific protease 9X (USP9X) contributes to genome stability during DNA replication and chromosome segregation. Depletion of USP9X leads to DNA double-strand breaks, some of which are triggered by replication fork collapse. Here, we identify USP9X as a novel regulator of homologous recombination (HR) DNA repair in human cells. By performing cellular HR reporter, irradiation-induced focus formation and colony formation assays, we show that USP9X is required for efficient HR. Mechanistically, we show USP9X is important to sustain the expression levels of key HR factors, namely BRCA1 and RAD51 through a non-canonical regulation of their mRNA abundance. Intriguingly, we find that the contribution of USP9X to BRCA1 and RAD51 expression is independent of its known catalytic activity. Thus, this work identifies USP9X as a regulator of HR, demonstrates a novel mechanism by which USP9X can regulate protein levels, and provides insights in to the regulation of BRCA1 and RAD51 mRNA.
This article has an associated First Person interview with the first author of the paper.
The gap junction protein connexin 43 controls multiple aspects of cranial neural crest cell development
Authors: Jourdeuil Karyn , Taneyhill Lisa A. 
Published: January 2020

ABSTRACT
Gap junctions are intercellular channels between cells that facilitate cell–cell communication. Connexin 43 (Cx43; also known as GJA1), the predominant gap junction protein in vertebrates, is expressed in premigratory cranial neural crest cells and is maintained throughout the neural crest cell epithelial-to-mesenchymal transition (EMT), but its function in these cells is unknown. To this end, we used a combination of in vivo and ex vivo experiments to assess gap junction formation, and Cx43 function, in chick cranial neural crest cells. Our results demonstrate that gap junctions exist between premigratory and migratory cranial neural crest cells and depend on Cx43 for their function. In the embryo, Cx43 knockdown just prior to EMT delays the emergence of Cx43-depleted neural crest cells from the neural tube, but these cells eventually successfully emigrate and join the migratory stream. This delay can be rescued by introduction of full-length Cx43 into Cx43-depleted cells. Furthermore, Cx43 depletion reduces the size of the premigratory neural crest cell domain through an early effect on neural crest cell specification. Collectively, these data identify new roles for Cx43 in chick cranial neural crest cell development.
DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis
Authors: van der Stoel Miesje , Schimmel Lilian , Nawaz Kalim , van Stalborch Anne-Marieke , de Haan Annett , Klaus-Bergmann Alexandra , Valent Erik T. , Koenis Duco S. , van Nieuw Amerongen Geerten P. , de Vries Carlie J. , de Waard Vivian , Gloerich Martijn , van Buul Jaap D. , Huveneers Stephan 
Published: January 2020

ABSTRACT
Endothelial YAP/TAZ (YAP is also known as YAP1, and TAZ as WWTR1) signaling is crucial for sprouting angiogenesis and vascular homeostasis. However, the underlying molecular mechanisms that explain how YAP/TAZ control the vasculature remain unclear. This study reveals that the focal adhesion protein deleted-in-liver-cancer 1 (DLC1) is a direct transcriptional target of the activated YAP/TAZ–TEAD complex. We find that substrate stiffening and VEGF stimuli promote expression of DLC1 in endothelial cells. In turn, DLC1 expression levels are YAP and TAZ dependent, and constitutive activation of YAP is sufficient to drive DLC1 expression. DLC1 is needed to limit F-actin fiber formation, integrin-based focal adhesion lifetime and integrin-mediated traction forces. Depletion of endothelial DLC1 strongly perturbs cell polarization in directed collective migration and inhibits the formation of angiogenic sprouts. Importantly, ectopic expression of DLC1 is sufficient to restore migration and angiogenic sprouting in YAP-depleted cells. Together, these findings point towards a crucial and prominent role for DLC1 in YAP/TAZ-driven endothelial adhesion remodeling and collective migration during angiogenesis.
This article has an associated First Person interview with the first author of the paper.
A critical review of the academic entrepreneurial ecosystem in developing countries: The case of Algeria
Authors: Chohra Mohamed 
Published: January 2020

Abstract
The objective of this article is to conduct a critical review of the literature related to the academic entrepreneurial ecosystems in developing countries in order to highlight the perspectives and to raise new questions in this area of research in these countries. The first part of this study examines the entrepreneurial context and innovation systems to determine the socio-economic and political factors that can have a negative influence on the emergence of an effective academic entrepreneurship in emerging economies. The second part explores the phenomenon of the academic entrepreneurial ecosystem in Algeria to identify the main issues and challenges that may have to be taken into consideration while promoting academic entrepreneurship in Algeria. In this study, we focus on the experience of the pharmaceutical industry as a successful model to develop effective approaches for commercializing the results of the academic research. The article also attempts to define the roles of three main actors, namely, the state, academic institutions and industry.
Style guide for an Open Access publishing workflow for academic books
Authors: Schrader Antonia , Böhm David , Grossmann Alexander , Reiche Michael 
Published: January 2020

The present style guide (Version 1.5 of October 10, 2019) has been created as result of the research project
Open-Access-Hochschulverlag (
Open Access University Press) at Leipzig University of Applied Sciences, Germany. The project was to develop a sustainable and adoptable workflow, which enables universities to publish their publications both as OA and printed books in a state-of-the-art publishing process and without any restrictions regarding the license, the variety of formats, print run etc. The style guide was created to characterise the internal layout of OA books, which have been published by our university press. To enable low-threshold transfer of knowledge how to publish OA books, this style guide has been published under Creative Commons Licence CC BY.
Publishing monographs in a uniformly series design, the so house style, offers several advantages: it creates a recognition value for the user, so the publications are better remembered and the university press as a publisher becomes more visible as a brand. In addition, a uniform appearance ensures a consistent quality standard, as scientific publications can be highly structured and complex. Strict specifications facilitate the handling of those complex content and ensures the uniform appearance.
The house style of our project consist of general specifications such as the selection of book formats, the basic structure of the scientific publication, page layout, baseline grids, fonts, colors, pagination and running titles, as well as rules for hyphenation and Document Object Identifier (DOI). Furthermore, specifications for the content-specific elements, which may occur in scientific publication are defined, such as heading hierarchies, footnotes, subtitles, lists and numbering, indents, formulas, source code, info boxes, figures and tables. Finally, the guideline includes further specifications, e.g. cover design, directories, appendix and specifications for the electronic output formats of the publication.
Murburn concept: a paradigm shift in cellular metabolism and physiology
Authors: Manoj Kelath Murali 
Published: January 2020

AbstractTwo decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept. Murburn is a novel literary abstraction from “muredburning” or “mildunrestrictedburning”. This concept was invoked to explain the longstanding conundrum of maverick physiological dose responses and also applied to remodel the prevailing understanding of drug metabolism and cellular respiration. A conglomeration of simple ideas grounded in the known principles of thermodynamics and reaction chemistry, murburn concept invokes catalytic/functional roles for diffusible reactive species or radicals. Hitherto, diffusible reactive species were primarily seen as toxic agents of chaos, non-conducible to the maintenance of life-order. Since the murburn paradigm offers a distinctly different perspective for several biological phenomena, researchers holding conventional views of cellular metabolism pose a direct conflict of interests to the advancement of murburn concept. Murburn schemes are poised to integrate numerous metabolic motifs with holistic physiological outcomes; redefining pursuits in biology and medicine. To advance this agenda, I present a brief account of murburn concept and point out how redundant ideas are still advocated in some prestigious journals.
The power of locality: Exploring the limits of randomness in distributed computing
Authors: Maus Yannic 
Published: January 2020

Abstract
Many modern systems are built on top of large-scale networks like the Internet. This article provides an overview of a dissertation [29] that addresses the complexity of classic graph problems like the vertex coloring problem in such networks. It has been known for a long time that randomization helps significantly in solving many of these problems, whereas the best known deterministic algorithms have been exponentially slower. In the first part of the dissertation we use a complexity theoretic approach to show that several problems are complete in the following sense: An efficient deterministic algorithm for any complete problem would imply an efficient algorithm for all problems that can be solved efficiently with a randomized algorithm. Among the complete problems is a rudimentary looking graph coloring problem that can be solved by a randomized algorithm without any communication. In further parts of the dissertation we develop efficient distributed algorithms for several problems where the most important problems are distributed versions of integer linear programs, the vertex coloring problem and the edge coloring problem. We also prove a lower bound on the runtime of any deterministic algorithm that solves the vertex coloring problem in a weak variant of the standard model of the area.
Investigations of the optical and electronic effects of silicon and indium co-doping on ZnO thin films deposited by spray pyrolysis
Authors: Fang Yiwen , Dilworth Jonathan R. , Pepper Michael , Edwards Peter P. 
Published: January 2020

Abstract
Silicon and indium co-doped ZnO thin films with both high optical and electrical performances have been successfully synthesised for the first time by the technique of spray pyrolysis. We find that this co-doping strategy can achieve comparable Figures-of-Merit performances to indium zinc oxide itself, but with, importantly, a significant saving in the indium content. The properties of the co-doped films are compared with those of either single indium or silicon doping.
Cognitive functioning in children with Prader–Willi syndrome during 8 years of growth hormone treatment
Authors: Donze S H , Damen L , Mahabier E F , Hokken-Koelega A C S 
Published: January 2020

Objective
Children with Prader–Willi syndrome (PWS) have mild to moderate cognitive impairment. Short-term studies showed positive effects of growth hormone (GH) on cognitive development. This study investigated the effects of 8 years of GH on cognitive development in children with PWS. We also investigated whether starting GH during infancy results in higher cognitive functioning after 8 years of GH.

Design
Longitudinal study in 43 children with PWS during 8 years of GH (median age at GH start 8.1 years). Cognitive functioning after 8 years was compared to another group of 22 children with PWS (median age at GH start 1.4 years).

Methods
Cognitive functioning was measured by Wechsler Intelligence Scale for Children. Vocabulary, Similarities and Block Design subtests were expressed as standard deviation scores (SDS) and total IQ (TIQ) calculated.

Results
Estimated mean (95%CI) Block Design SDS changed from −2.2 (−2.6; −1.8) at GH start to −1.8 (−2.2; −1.4) after 8 years of GH (P = 0.18), similarly SDS from −1.5 (−2.1; −0.9) to −1.3 (−1.9; −0.7, P = 0.66) and TIQ from 66 (60; 72) to 69 (63; 75, P = 0.57). Vocabulary SDS remained similar, being −1.9 (−2.3; −1.4) at GH start and −1.9 (−2.4; −1.5) after 8 years (P = 0.85). After 8 years of GH Vocabulary, SDS and TIQ were higher in the children who started GH during infancy, compared to those who started GH later in childhood (P < 0.01, P = 0.04, respectively).

Conclusions
Cognitive functioning in children with PWS remains similar during long-term GH and develops at the same pace as healthy peers.
Anthropometric and biochemical correlates of PAPP-A2, free IGF-I, and IGFBP-3 in childhood
Authors: Fujimoto Masanobu , Khoury Jane C , Khoury Philip R , Kalra Bhanu , Kumar Ajay , Sluss Patrick , Oxvig Claus , Hwa Vivian , Dauber Andrew 
Published: January 2020

Objective
Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low percentage of free IGF-I. Little is known about PAPP-A2 levels and the regulation of free IGF-I throughout childhood. We examined PAPP-A2 and intact IGFBP-3 levels in childhood and explored associations between PAPP-A2, free and total IGF-I, and total and intact IGFBP-3 and their relationship to the percentage of free to total IGF-I and anthropometric factors.

Design
Cross-sectional study at a single center.

Methods
PAPP-A2, free IGF-I, and intact IGFBP-3 levels were measured in childhood (3–18 years old) and an evaluation of the relationship between these proteins and anthropometric factors.

Results
In 838 children, PAPP-A2 consistently decreased throughout childhood. In contrast, free IGF-I increased. A pubertal peak in free IGF-I was present in females but was less evident in males. Intact and total IGFBP-3 increased throughout childhood; however, intact IGFBP-3 had a more marked rise than total IGFBP-3. Percent free IGF-I decreased with no distinct pubertal peak. PAPP-A2 levels positively correlated with the percent free IGF-I (Male, Female; r = 0.18, 0.38; P < 0.001) and negatively with intact IGFBP-3 (Male, Female; r = −0.58, −0.65; P < 0.0001).

Conclusions
This is the first study to describe serum PAPP-A2 and intact IGFBP-3 in children between 3 and 18 years of age. Our correlative findings suggest that PAPP-A2 is an important regulator of the percent free IGF-I which can be a marker of perturbations in the GH/IGF-I axis.
Investigating the Generic Features of the Sudanese Judicial Precedents
Authors: Elhassan Yasir Mohamed Mohamed 
Published: January 2020

This study aims at investigating the Sudanese criminal and civil judicial precedents so as to gain a better understanding of the communicative purposes of each subgenre and the variation in demands across the two subgenres using genre analysis. It adopted the mixed approach, using Maxqda application, to investigate the generic features, the moves, the sub-moves; as well as how problems are solved and decisions arrived at. The investigation shows that the law practitioners should know the intrinsic nature of these judicial precedents by examining their generic features, concepts, functions and approaches. Also, the analysis of the typical generic moves and sub-moves clearly reveals that the judicial precedents across the two subgenres have some overlapping generic structures at all levels. Most of the judicial precedents in the corpus seem to have the typical generic move structures. The analysis of the specific generic move structures reveals slight generic differences of judicial precedents. Finally, there are still evidences of slight variation across the two subgenres at sub-move level.
A “banalidade do mal” e a educação enquanto promotora dos direitos humanos
Authors: Barbosa Gabriela De Lima , Pereira Gilvan Elias 
Published: January 2020

A incapacidade de o sujeito analisar criticamente as consequências de suas ações enquanto as realiza por meio da obediência plena e acrítica a um código de ética pré-estabelecido socialmente é uma das características daquilo que Hannah Arendt chamou, no início da década de 1960, de “banalidade do mal”. Entende-se, neste trabalho, que este fenômeno de “naturalização do mal” se faz presente, atualmente, sempre que diversos interesses e ações se sobrepõem aos valores humanos estabelecidos na Declaração Universal dos Direitos Humanos (1948) de modo a propiciar situações diversas de desrespeito à dignidade humana. Entende-se, ainda, que para que os direitos humanos sejam prioridade de uma nação, se faz necessário, dentre outras coisas, que a educação assuma uma perspectiva emancipadora do sujeito educativo. Diante do exposto, este artigo levanta o seguinte questionamento: em que medida a educação pode ser um meio para a emancipação do educando de modo a favorecer que o mesmo se torne sujeito conhecedor e reivindicador de seus direitos? A partir de estudos bibliográficos conclui-se que à medida que o sujeito toma para si os direitos fundamentais da pessoa humana como princípios norteadores de suas ações, das mais corriqueiras às mais atípicas, grande parte das violações à dignidade do ser humano são atenuadas
The 30 June 2017 North Sea Earthquake: Location, Characteristics, and Context
Authors: Jerkins Annie E. , Shiddiqi Hasbi Ash , Kværna Tormod , Gibbons Steven J. , Schweitzer Johannes , Ottemöller Lars , Bungum Hilmar 
Published: January 2020

ABSTRACTThe Mw 4.5 southern Viking graben earthquake on 30 June 2017 was one of the largest seismic events in the Norwegian part of the North Sea during the last century. It was well recorded on surrounding broadband seismic stations at regional distances, and it generated high signal-to-noise ratio teleseismic P arrivals at up to 90° with good azimuthal coverage. Here, the teleseismic signals provide a unique opportunity to constrain the event hypocenter. Depth phases are visible globally and indicate a surface reflection in the P-wave coda some 4 s after the initial P arrival, giving a much better depth constraint than regional S-P time differences provide. Moment tensor inversion results in a reverse thrust faulting mechanism. The fit between synthetic and observed surface waves at regional distances is improved by including a sedimentary layer. Synthetic teleseismic waveforms generated based on the moment tensor solution, and a near-source 1D velocity model indicates a depth of 7 km. Correlation detectors using the S-wave coda from the main event were run on almost 30 yr of continuous multichannel seismic data searching for repeating signals. In addition to a magnitude 1.9 aftershock 33 min later, and a few magnitude ∼1 events in the following days, a magnitude 2.5 earthquake on 13 November 2016 was the only event found to match the 30 June 2017 event well. Using double-difference techniques, we find that the two largest events are located within 1 km of the main event. We present a Bayesloc probabilistic multiple event location including the 30 June event and all additional seismic events in the region well recorded on the regional networks. The Bayesloc relocation gave a more consistent seismicity pattern and moved several of the events more toward the west. The results of this study are also discussed within the regional seismotectonic frame of reference.
Exploring long-term youth unemployment in Europe using sequence analysis: a reproducible notebook approach
Authors: Patias Nikos 
Published: January 2020

Youth unemployment is a factor influencing European policy. The effects of financial crisis of 2008 in youth unemployment were prominent and varied across European countries and regions. This notebook aims to identify key representative trajectories of youth unemployment by NUTS 2 regions in Europe from 2008 to 2018. Moreover, this notebook provides a self-contained research workflow that is fully reproducible and transparent, using a wide range of functionalities offered by computational notebooks. The results show that there is a divide between northern and southern regions. Northern regions follow stable low youth unemployment levels, while southern regions follow stable high youth unemployment levels. Finally, the results show that there are patterns of regional inequalities between major metropolitan areas and their adjacent regions.