bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirements elicitation and refinement in collaborative research projects
Authors: De Angelis Guglielmo , Ferrari Alessio , Gnesi Stefania , Polini Andrea 
Published: December 2018

SummaryEuropean Union (EU) projects are means of the European Commission for funding research activities. Such projects address challenging research objectives by involving both academic and industrial partners, from several countries. Information and communication technologies–related projects often undertake to deliver a software system prototype. In such a context, most of the typical issues of global requirements engineering may emerge. Partners can have different background and expertise, needs are not sharply defined, and communication is hampered by linguistic and cultural differences. If these issues are not carefully taken into account from the beginning, problems frequently emerge during project execution. This paper presents the experience of applying a customized elicitation and refinement approach in the context of the Learn PAd EU project, which involved about 50 people. The approach combines collaborative elicitation and wiki‐based refinement sessions to come to a set of consolidated requirements. Lessons learnt are discussed as a guidance for researchers dealing with analogous issues in similar contexts. Some of the major observations refer to the importance of initial face‐to‐face meetings when combined with asynchronous remote interactions; the role of moderators that have to encourage collaboration and foster a shared understanding; and the definition of guidelines to select wiki‐based platforms.
Reading as a source of knowledge
Authors: van Woudenberg René 
Published: December 2018

AbstractThis paper argues that reading is a source of knowledge. Epistemologists have virtually ignored reading as a source of knowledge. This paper argues, first, that reading is not to be equated with attending to testimony, and second that it cannot be reduced to perception. Next an analysis of reading is offered and the source of knowledge that reading is further delineated. Finally it is argued that the source that reading is, can be both transmissive and generative, is non-basic, once was a non-essential but has become essential for many people, and can be unique.
GITAR: An Open Source Tool for Analysis and Visualization of Hi-C Data
Authors: Calandrelli Riccardo , Wu Qiuyang , Guan Jihong , Zhong Sheng 
Published: December 2018

Abstract
Interactions between chromatin segments play a large role in functional genomic assays and developments in genomic interaction detection methods have shown interacting topological domains within the genome. Among these methods, Hi-C plays a key role. Here, we present the Genome Interaction Tools and Resources (GITAR), a software to perform a comprehensive Hi-C data analysis, including data preprocessing, normalization, and visualization, as well as analysis of topologically-associated domains (TADs). GITAR is composed of two main modules: (1) HiCtool, a Python library to process and visualize Hi-C data, including TAD analysis; and (2) processed data library, a large collection of human and mouse datasets processed using HiCtool. HiCtool leads the user step-by-step through a pipeline, which goes from the raw Hi-C data to the computation, visualization, and optimized storage of intra-chromosomal contact matrices and TAD coordinates. A large collection of standardized processed data allows the users to compare different datasets in a consistent way, while saving time to obtain data for visualization or additional analyses. More importantly, GITAR enables users without any programming or bioinformatic expertise to work with Hi-C data. GITAR is publicly available at http://genomegitar.org as an open-source software.
Development of the “Third-Generation” Hybrid Rice in China
Authors: Wang Haiyang , Deng Xing Wang 
Published: December 2018

Abstract
Rice is a major cereal crop for China. The development of the “three-line” hybrid rice system based on cytoplasmic male sterility in the 1970s (first-generation) and the “two-line” hybrid rice system based on photoperiod- and thermo-sensitive genic male-sterile lines (second-generation) in the 1980s has contributed significantly to rice yield increase and food security in China. Here we describe the development and implementation of the “third-generation” hybrid rice breeding system that is based on a transgenic approach to propagate and utilize stable recessive nuclear male sterile lines, and as such, the male sterile line and hybrid rice produced using such a system is non-transgenic. Such a system should overcome the intrinsic problems of the “first-generation” and “second-generation” hybrid rice systems and hold great promise to further boost production of hybrid rice and other crops.
Alzheimer's disease in Down syndrome: An overlooked population for prevention trials
Authors: Strydom André , Coppus Antonia , Blesa Rafael , Danek Adrian , Fortea Juan , Hardy John , Levin Johannes , Nuebling Georg , Rebillat Anne‐Sophie , Ritchie Craig , van Duijn Cornelia , Zaman Shahid , Zetterberg Henrik 
Published: December 2018

AbstractThe discovery that adults with Down syndrome (DS) have neuropathological features identical to individuals with sporadic Alzheimer's disease (AD) played a key role in the identification of the amyloid precursor protein gene on chromosome 21 and resulted in the amyloid cascade hypothesis. Individuals with DS have a lifetime risk for dementia in excess of 90%, and DS is now acknowledged to be a genetic form of AD similar to rare autosomal‐dominant causes. Just as DS put the spotlight on amyloid precursor protein mutations, it is also likely to inform us of the impact of manipulating the amyloid pathway on treatment outcomes in AD. Ironically, however, individuals with DS are usually excluded from AD trials. This review will discuss primary and secondary prevention trials for AD in DS and the potential barriers and solutions to such trials and describe the Europe‐wide Horizon21 Consortium to establish a DS‐AD prevention clinical trials network.
Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa
Authors: Olivo Gaia , Swenne Ingemar , Zhukovsky Christina , Tuunainen Anna-Kaisa , Salonen-Ros Helena , Larsson Elna-Marie , Gaudio Santino , Brooks Samantha J. , Schiöth Helgi B. 
Published: December 2018

AbstractAtypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naïve adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery–Åsberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.
Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM
Authors: Przystal Justyna Magdalena , Hajji Nabil , Khozoie Combiz , Renziehausen Alexander , Zeng Qingyu , Abaitua Fernando , Hajitou Amin , Suwan Keittisak , Want Elizabeth , Bomalaski John , Szlosarek Peter , O’Neill Kevin , Crook Tim , Syed Nelofer 
Published: December 2018

AbstractGlioblastoma multiforme (GBM) remains a cancer with a poor prognosis and few effective therapeutic options. Successful medical management of GBM is limited by the restricted access of drugs to the central nervous system (CNS) caused by the blood brain barrier (BBB). We previously showed that a subset of GBM are arginine auxotrophic because of transcriptional silencing ofASS1and/orASLand are sensitive to pegylated arginine deiminase (ADI-PEG20). However, it is unknown whether depletion of arginine in peripheral blood in vivo has therapeutic activity against intracranial disease. In the present work, we describe the efficacy of ADI-PEG20 in an intracranial model of human GBM in which tumour growth and regression are assessed in real time by measurement of luciferase activity. Animals bearing intracranial human GBM tumours of varying ASS status were treated with ADI-PEG20 alone or in combination with temozolomide and monitored for tumour growth and regression. Monotherapy ADI-PEG20 significantly reduces the intracranial growth of ASS1 negative GBM and extends survival of mice carrying ASS1 negative GBM without obvious toxicity. The combination of ADI-PEG20 with temozolomide (TMZ) demonstrates enhanced effects in both ASS1 negative and ASS1 positive backgrounds.Our data provide proof of principle for a therapeutic strategy for GBM using peripheral blood arginine depletion that does not require BBB passage of drug and is well tolerated. The ability of ADI-PEG20 to cytoreduce GBM and enhance the effects of temozolomide argues strongly for its early clinical evaluation in the treatment of GBM.
Cleaning interfaces in layered materials heterostructures
Authors: Purdie D. G. , Pugno N. M. , Taniguchi T. , Watanabe K. , Ferrari A. C. , Lombardo A. 
Published: December 2018

AbstractHeterostructures formed by stacking layered materials require atomically clean interfaces. However, contaminants are usually trapped between the layers, aggregating into randomly located blisters, incompatible with scalable fabrication processes. Here we report a process to remove blisters from fully formed heterostructures. Our method is over an order of magnitude faster than those previously reported and allows multiple interfaces to be cleaned simultaneously. We fabricate blister-free regions of graphene encapsulated in hexagonal boron nitride with an area ~ 5000 μm2, achieving mobilities up to 180,000 cm2 V−1 s−1 at room temperature, and 1.8 × 106 cm2 V−1 s−1 at 9 K. We also assemble heterostructures using graphene intentionally exposed to polymers and solvents. After cleaning, these samples reach similar mobilities. This demonstrates that exposure of graphene to process-related contaminants is compatible with the realization of high mobility samples, paving the way to the development of wafer-scale processes for the integration of layered materials in (opto)electronic devices.
High-resolution genome-wide functional dissection of transcriptional regulatory regions and nucleotides in human
Authors: Wang Xinchen , He Liang , Goggin Sarah M. , Saadat Alham , Wang Li , Sinnott-Armstrong Nasa , Claussnitzer Melina , Kellis Manolis 
Published: December 2018

AbstractGenome-wide epigenomic maps have revealed millions of putative enhancers and promoters, but experimental validation of their function and high-resolution dissection of their driver nucleotides remain limited. Here, we present HiDRA (High-resolution Dissection of Regulatory Activity), a combined experimental and computational method for high-resolution genome-wide testing and dissection of putative regulatory regions. We test ~7 million accessible DNA fragments in a single experiment, by coupling accessible chromatin extraction with self-transcribing episomal reporters (ATAC-STARR-seq). By design, fragments are highly overlapping in densely-sampled accessible regions, enabling us to pinpoint driver regulatory nucleotides by exploiting differences in activity between partially-overlapping fragments using a machine learning model (SHARPR-RE). In GM12878 lymphoblastoid cells, we find ~65,000 regions showing enhancer function, and pinpoint ~13,000 high-resolution driver elements. These are enriched for regulatory motifs, evolutionarily-conserved nucleotides, and disease-associated genetic variants from genome-wide association studies. Overall, HiDRA provides a high-throughput, high-resolution approach for dissecting regulatory regions and driver nucleotides.
Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance
Authors: Chacón-Duque Juan-Camilo , Adhikari Kaustubh , Fuentes-Guajardo Macarena , Mendoza-Revilla Javier , Acuña-Alonzo Victor , Barquera Rodrigo , Quinto-Sánchez Mirsha , Gómez-Valdés Jorge , Everardo Martínez Paola , Villamil-Ramírez Hugo , Hünemeier Tábita , Ramallo Virginia , Silva de Cerqueira Caio C. , Hurtado Malena , Villegas Valeria , Granja Vanessa , Villena Mercedes , Vásquez René , Llop Elena , Sandoval José R. , Salazar-Granara Alberto A. , Parolin Maria-Laura , Sandoval Karla , Peñaloza-Espinosa Rosenda I. , Rangel-Villalobos Hector , Winkler Cheryl A. , Klitz William , Bravi Claudio , Molina Julio , Corach Daniel , Barrantes Ramiro , Gomes Verónica , Resende Carlos , Gusmão Leonor , Amorim Antonio , Xue Yali , Dugoujon Jean-Michel , Moral Pedro , González-José Rolando , Schuler-Faccini Lavinia , Salzano Francisco M. , Bortolini Maria-Cátira , Canizales-Quinteros Samuel , Poletti Giovanni , Gallo Carla , Bedoya Gabriel , Rothhammer Francisco , Balding David , Hellenthal Garrett , Ruiz-Linares Andrés 
Published: December 2018

AbstractHistorical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.
PI3Kα-regulated gelsolin activity is a critical determinant of cardiac cytoskeletal remodeling and heart disease
Authors: Patel Vaibhav B. , Zhabyeyev Pavel , Chen Xueyi , Wang Faqi , Paul Manish , Fan Dong , McLean Brent A. , Basu Ratnadeep , Zhang Pu , Shah Saumya , Dawson John F. , Pyle W. Glen , Hazra Mousumi , Kassiri Zamaneh , Hazra Saugata , Vanhaesebroeck Bart , McCulloch Christopher A. , Oudit Gavin Y. 
Published: December 2018

AbstractBiomechanical stress and cytoskeletal remodeling are key determinants of cellular homeostasis and tissue responses to mechanical stimuli and injury. Here we document the increased activity of gelsolin, an actin filament severing and capping protein, in failing human hearts. Deletion of gelsolin prevents biomechanical stress-induced adverse cytoskeletal remodeling and heart failure in mice. We show that phosphatidylinositol (3,4,5)-triphosphate (PIP3) lipid suppresses gelsolin actin-severing and capping activities. Accordingly, loss of PI3Kα, the key PIP3-producing enzyme in the heart, increases gelsolin-mediated actin-severing activities in the myocardium in vivo, resulting in dilated cardiomyopathy in response to pressure-overload. Mechanical stretching of adult PI3Kα-deficient cardiomyocytes disrupts the actin cytoskeleton, which is prevented by reconstituting cells with PIP3. The actin severing and capping activities of recombinant gelsolin are effectively suppressed by PIP3. Our data identify the role of gelsolin-driven cytoskeletal remodeling in heart failure in which PI3Kα/PIP3 act as negative regulators of gelsolin activity.
Emerging negative impact of warming on summer carbon uptake in northern ecosystems
Authors: Wang Tao , Liu Dan , Piao Shilong , Wang Yilong , Wang Xiaoyi , Guo Hui , Lian Xu , Burkhart John F , Ciais Philippe , Huang Mengtian , Janssens Ivan , Li Yue , Liu Yongwen , Peñuelas Josep , Peng Shushi , Yang Hui , Yao Yitong , Yin Yi , Zhao Yutong 
Published: December 2018

AbstractMost studies of the northern hemisphere carbon cycle based on atmospheric CO2concentration have focused on spring and autumn, but the climate change impact on summer carbon cycle remains unclear. Here we used atmospheric CO2record from Point Barrow (Alaska) to show that summer CO2drawdown between July and August, a proxy of summer carbon uptake, is significantly negatively correlated with terrestrial temperature north of 50°N interannually during 1979–2012. However, a refined analysis at the decadal scale reveals strong differences between the earlier (1979–1995) and later (1996–2012) periods, with the significant negative correlation only in the later period. This emerging negative temperature response is due to the disappearance of the positive temperature response of summer vegetation activities that prevailed in the earlier period. Our finding, together with the reported weakening temperature control on spring carbon uptake, suggests a diminished positive effect of warming on high-latitude carbon uptake.
Topological one-way fiber of second Chern number
Authors: Lu Ling , Gao Haozhe , Wang Zhong 
Published: December 2018

AbstractOne-way waveguides have been discovered as topological edge states in two-dimensional (2D) photonic crystals. Here, we design one-way fiber modes in a 3D magnetic Weyl photonic crystal realizable at microwave frequencies. We first obtain a 3D Chern crystal with a non-zero first Chern number by annihilating the Weyl points through supercell modulation. When the modulation becomes helixes, one-way modes develop along the winding axis, with the number of modes determined by the spatial frequency of the helix. These single-polarization single-mode and multi-mode one-way fibers, having nearly identical group and phase velocities, are topologically-protected by the second Chern number in the 4D parameter space of the 3D wavevectors plus the winding angle of the helix. This work suggests a unique way to utilize high-dimensional topological physics using topological defects.
Closure of the Bering Strait caused Mid-Pleistocene Transition cooling
Authors: Kender Sev , Ravelo Ana Christina , Worne Savannah , Swann George E. A. , Leng Melanie J. , Asahi Hirofumi , Becker Julia , Detlef Henrieka , Aiello Ivano W. , Andreasen Dyke , Hall Ian R. 
Published: December 2018

AbstractThe Mid-Pleistocene Transition (MPT) is characterised by cooling and lengthening glacial cycles from 600–1200 ka, thought to be driven by reductions in glacial CO2 in particular from ~900 ka onwards. Reduced high latitude upwelling, a process that retains CO2 within the deep ocean over glacials, could have aided drawdown but has so far not been constrained in either hemisphere over the MPT. Here, we find that reduced nutrient upwelling in the Bering Sea, and North Pacific Intermediate Water expansion, coincided with the MPT and became more persistent at ~900 ka. We propose reduced upwelling was controlled by expanding sea ice and North Pacific Intermediate Water formation, which may have been enhanced by closure of the Bering Strait. The regional extent of North Pacific Intermediate Water across the subarctic northwest Pacific would have contributed to lower atmospheric CO2 and global cooling during the MPT.
Exploring the rumen fluid metabolome using liquid chromatography-high-resolution mass spectrometry and Molecular Networking
Authors: de Almeida Rafaela Takako Ribeiro , do Prado Rodolpho Martin , Porto Carla , dos Santos Geraldo Tadeu , Huws Sharon Ann , Pilau Eduardo Jorge 
Published: December 2018

AbstractThe rumen primary and secondary metabolite content is intimately related to its community of bacteria, protozoa, fungi, archaea and bacteriophages, ingested feed and the host. Despite the myriad of interactions and novel compounds to be discovered, few studies have explored the rumen metabolome. Here, we present the first study using ultra-high performance liquid chromatography tandem mass-spectrometry and Molecular Networking approach, and various extraction methods on the cell-free rumen fluid of a non-lactating Holstein cow. Putative molecules were annotated based on accurate fragmentation matching the Global Natural Products Social Molecular Networking library, public spectral libraries, or annotated manually. The combination of five extraction methods resulted on 1,882 molecular features observed. Liquid-liquid extraction resulted on the highest molecular features abundance, 1,166 (61.96% of total). Sixty-seven compounds were annotated using Global Natural Products Social Molecular Networking library and public libraries, such as hydrocinnamic and azelaic acid, and monensin. Only 3.56% of molecular features (67) observed had positive match with available libraries, which shows the potential of the rumen as reservoir of novel compounds. The use of untargeted metabolomics in this study provided a snapshot of the rumen fluid metabolome. The complexity of the rumen will remain long unknown, but the use of new tools should be encouraged to foster advances on the rumen metabolome.
Relation between mitochondrial DNA hyperdiversity, mutation rate and mitochondrial genome evolution in Melarhaphe neritoides (Gastropoda: Littorinidae) and other Caenogastropoda
Authors: Fourdrilis Séverine , de Frias Martins Antonio M. , Backeljau Thierry 
Published: December 2018

AbstractMitochondrial DNA hyperdiversity is primarily caused by high mutation rates (µ) and has potential implications for mitogenome architecture and evolution. In the hyperdiverse mtDNA ofMelarhaphe neritoides(Gastropoda: Littorinidae), high mutational pressure generates unusually large amounts of synonymous variation, which is expected to (1) promote changes in synonymous codon usage, (2) reflect selection at synonymous sites, (3) increase mtDNA recombination and gene rearrangement, and (4) be correlated with high mtDNA substitution rates. The mitogenome ofM. neritoideswas sequenced, compared to closely related littorinids and put in the phylogenetic context of Caenogastropoda, to assess the influence of mtDNA hyperdiversity and highµon gene content and gene order. Most mitogenome features are in line with the trend in Mollusca, except for the atypical secondary structure of the methionine transfer RNA lacking the TΨC-loop. Therefore, mtDNA hyperdiversity and highµinM. neritoidesdo not seem to affect its mitogenome architecture. Synonymous sites are under positive selection, which adds to the growing evidence of non-neutral evolution at synonymous sites. Under such non-neutrality, substitution rate involves neutral and non-neutral substitutions, and highµis not necessarily associated with high substitution rate, thus explaining that, unlike highµ, a high substitution rate is associated with gene order rearrangement.