bluuebunny/crossref_metadata_2025_split huggingface dataset:
From complex data to biological insight: ‘DEKER’ feature selection and network inference
Authors: Hayes Sean M. S. , Sachs Jeffrey R. , Cho Carolyn R. 
Published: November 2021

AbstractNetwork inference is a valuable approach for gaining mechanistic insight from high-dimensional biological data. Existing methods for network inference focus on ranking all possible relations (edges) among all measured quantities such as genes, proteins, metabolites (features) observed, which yields a dense network that is challenging to interpret. Identifying a sparse, interpretable network using these methods thus requires an error-prone thresholding step which compromises their performance. In this article we propose a new method, DEKER-NET, that addresses this limitation by directly identifying a sparse, interpretable network without thresholding, improving real-world performance. DEKER-NET uses a novel machine learning method for feature selection in an iterative framework for network inference. DEKER-NET is extremely flexible, handling linear and nonlinear relations while making no assumptions about the underlying distribution of data, and is suitable for categorical or continuous variables. We test our method on the Dialogue for Reverse Engineering Assessments and Methods (DREAM) challenge data, demonstrating that it can directly identify sparse, interpretable networks without thresholding while maintaining performance comparable to the hypothetical best-case thresholded network of other methods.
The Aesthetics of the Human Beast: A Comparative Study of Zola’s L’Assommoir, Galdós’ La Desheredada and Crane’s Maggie
Authors: Valentová Kateřina 
Published: November 2021

AbstractThe concept of the human beast is assigned to the French novelist, Émile Zola, who is the first to codify principles of Naturalism, against which all future naturalist works would be compared. In his novels, especially in the saga Les Rougon-Macquart, the human beast, «la bête humaine», appears as a literary character embedded in the lower social strata, who, due to harsh working and living conditions in the French capital during the Second Empire, acts according to its most basic instincts. The actions of a human beast are violent and brutal and its behavior conditioned by limited education. In his novels, Zola applies the doctrines of biological determinism as well as the laws of heredity attained from scientific readings that were very popular among the intellectuals of the period. However, the theoretical principles recollected in Le roman expérimental (G. Charpentier et Cie Éditeurs, 1880) were not equally applied in other countries due to different literary precedents as well as diverse socio-historical and philosophical backgrounds. This paper aims to examine the nuances in the aesthetic representation of the human beast in Zola’s L’Assommoir (1877), Galdós’ La Desheredada (1881) and Crane’s Maggie, a Girl of the Streets (1843), delving into the behavioral patterns which shape the unique characteristics of their human beasts.
Localized stationary seismic waves predicted using a nonlinear gradient elasticity model
Authors: Dostal Leo , Hollm Marten , Metrikine Andrei V. , Tsouvalas Apostolos , van Dalen Karel N. 
Published: November 2021

AbstractThis paper aims at investigating the existence of localized stationary waves in the shallow subsurface whose constitutive behavior is governed by the hyperbolic model, implying non-polynomial nonlinearity and strain-dependent shear modulus. To this end, we derive a novel equation of motion for a nonlinear gradient elasticity model, where the higher-order gradient terms capture the effect of small-scale soil heterogeneity/micro-structure. We also present a novel finite-difference scheme to solve the nonlinear equation of motion in space and time. Simulations of the propagation of arbitrary initial pulses clearly reveal the influence of the nonlinearity: strain-dependent speed in general and, as a result, sharpening of the pulses. Stationary solutions of the equation of motion are obtained by introducing the moving reference frame together with the stationarity assumption. Periodic (with and without a descending trend) as well as localized stationary waves are found by analyzing the obtained ordinary differential equation in the phase portrait and integrating it along the different trajectories. The localized stationary wave is in fact a kink wave and is obtained by integration along a homoclinic orbit. In general, the closer the trajectory lies to a homoclinic orbit, the sharper the edges of the corresponding periodic stationary wave and the larger its period. Finally, we find that the kink wave is in fact not a true soliton as the original shapes of two colliding kink waves are not recovered after interaction. However, it may have high amplitude and reach the surface depending on the damping mechanisms (which have not been considered). Therefore, seismic site response analyses should not a priori exclude the presence of such localized stationary waves.
Determining leaf nutrient concentrations in citrus trees using UAV imagery and machine learning
Authors: Costa Lucas , Kunwar Sudip , Ampatzidis Yiannis , Albrecht Ute 
Published: November 2021

AbstractNutrient assessment of plants, a key aspect of agricultural crop management and varietal development programs, traditionally is time demanding and labor-intensive. This study proposes a novel methodology to determine leaf nutrient concentrations of citrus trees by using unmanned aerial vehicle (UAV) multispectral imagery and artificial intelligence (AI). The study was conducted in four different citrus field trials, located in Highlands County and in Polk County, Florida, USA. In each location, trials contained either ‘Hamlin’ or ‘Valencia’ sweet orange scion grafted on more than 30 different rootstocks. Leaves were collected and analyzed in the laboratory to determine macro- and micronutrient concentration using traditional chemical methods. Spectral data from tree canopies were obtained in five different bands (red, green, blue, red edge and near-infrared wavelengths) using a UAV equipped with a multispectral camera. The estimation model was developed using a gradient boosting regression tree and evaluated using several metrics including mean absolute percentage error (MAPE), root mean square error, MAPE-coefficient of variance (CV) ratio and difference plot. This novel model determined macronutrients (nitrogen, phosphorus, potassium, magnesium, calcium and sulfur) with high precision (less than 9% and 17% average error for the ‘Hamlin’ and ‘Valencia’ trials, respectively) and micro-nutrients with moderate precision (less than 16% and 30% average error for ‘Hamlin’ and ‘Valencia’ trials, respectively). Overall, this UAV- and AI-based methodology was efficient to determine nutrient concentrations and generate nutrient maps in commercial citrus orchards and could be applied to other crop species.
Hypoxia modulates human mast cell adhesion to hyaluronic acid
Authors: Pastwińska Joanna , Walczak-Drzewiecka Aurelia , Kozłowska Elżbieta , Harunari Enjuro , Ratajewski Marcin , Dastych Jarosław 
Published: November 2021

AbstractHypoxia is an inherent factor in the inflammatory process and is important in the regulation of some immune cell functions, including the expression of mast cell pro- and anti-inflammatory mediators. Hypoxia also influences cell adhesion to the extracellular matrix (ECM). Hyaluronic acid is one of the major components of the ECM that is involved in inflammatory and tissue regeneration processes in which mast cells play a prominent role. This prompted us to investigate the effects of hypoxia on the expression of hyaluronic acid receptors in mast cells and mast cell adhesion to this ECM component. We found that human LAD2 mast cells spontaneously adhered to hyaluronic acid in a CD44-dependent manner and that reduced oxygen concentrations inhibited or even completely abolished this adhesion process. The mechanism of hypoxia downregulation of mast cell adhesion to hyaluronic acid did not involve a decrease in CD44 expression and hyaluronidase-mediated degradation of adhesion substrates but rather conformational changes in the avidity of CD44 to hyaluronic acid. Hypoxia-mediated regulation of mast cell adhesion to extracellular matrix components might be involved in the pathogenic accumulation of mast cells observed in the course of certain diseases including rheumatoid arthritis and cancer.
Chemical Fingerprint of Non-aged Artisanal Sugarcane Spirits Using Kohonen Artificial Neural Network
Authors: Caetano Daniela , Gonçalves Lima Clara Mariana , Lima Sanson Ananda , Faria Silva Debora , de Souza Hassemer Guilherme , Verruck Silvani , Gregorio Sandra Regina , da Silva Gilmare Antonia , de Cassia Franco Afonso Robson Jose , Xavier Coutrim Mauricio , El-Saber Batiha Gaber , Simal-Gandara Jesus 
Published: November 2021

Abstract
This study focuses on the determination of the chemical profile of 24 non-aged Brazilian artisanal sugarcane spirits (cachaça) samples through chromatographic quantification and chemometric treatment via principal component analysis (PCA) and Kohonen’s neural network. In total, forty-seven (47) chemical compounds were identified in the samples of non-aged artisanal cachaça, in addition to determining alcohol content, volatile acidity, and copper. For the PCA of the chemical compounds’ profile, it could be observed that the samples were grouped into seven groups. On the other hand, the variables’ bearings were grouped together, making it difficult to separate the components in relation to the sample groups and reducing the chances of obtaining all the necessary information. However, by using a Kohonen’s neural network, samples were grouped into eight groups. This tool proved to be more accurate in the groups’ formation. Among the chemical classes of the compounds observed, esters stood out, followed by alcohols, acids, aldehydes, ketones, phenol, and copper. The abundance of esters in these samples may suggest that these compounds would be part of the regional standard for cachaças produced in the region of Salinas, Minas Gerais.
Climate Change and Non-Identity
Authors: Tank Lukas 
Published: November 2021

AbstractWhat is the practical relevance of the Non-Identity Problem (NIP) for our climate change-related duties? Climate change and the NIP are often discussed together, but there is surprisingly little work on the practical relevance of the NIP for the ethics of climate change. The central claim of this article is that the NIP makes a relatively minor difference to our climate change-related duties even if we pursue what has become known as the ‘bite the bullet’ strategy: endorse a person-affecting view threatened by the NIP and not modify it in such a way as to evade the NIP. In particular I will argue that a harm-based view can justify the big-picture call for action emerging from the field of climate ethics. The key to reaching this conclusion is pointing out the consequences of our climate change-related decisions for people whose existence does not depend on these very decisions.
Diel Redox Cycle of Manganese in the Surface Arctic Ocean
Authors: Xiang Y. , Lam P. J. , Lee J. M. 
Published: November 2021

AbstractKnowledge of the chemical speciation of particulate manganese (pMn) is important for understanding the biogeochemical cycling of Mn and other particle‐reactive elements. Here, we present the synchrotron‐based X‐ray spectroscopy‐derived average oxidation state (AOS) of pMn in the surface Arctic Ocean collected during the United States GEOTRACES Arctic cruise (GN01) in 2015. We show that the pMn AOS is <2.4 when sampled during the day and more than ∼3.0 when sampled at night. We hypothesize that an active light‐dependent redox cycle between dissolved Mn and particulate Mn(III/IV) exists during the day‐night cycle in the surface Arctic Ocean, which occurs on the timescale of hours. The magnitude of observed pMn AOS is likely determined by the net effect of the length of the previous night and integrated light level before the end of pMn sampling.
Schizophrenia is defined by cell-specific neuropathology and multiple neurodevelopmental mechanisms in patient-derived cerebral organoids
Authors: Notaras Michael , Lodhi Aiman , Dündar Friederike , Collier Paul , Sayles Nicole M. , Tilgner Hagen , Greening David , Colak Dilek 
Published: November 2021

AbstractDue to an inability to ethically access developing human brain tissue as well as identify prospective cases, early-arising neurodevelopmental and cell-specific signatures of Schizophrenia (Scz) have remained unknown and thus undefined. To overcome these challenges, we utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids to model neuropathology of Scz during this critical period. We discovered that Scz organoids exhibited ventricular neuropathology resulting in altered progenitor survival and disrupted neurogenesis. This ultimately yielded fewer neurons within developing cortical fields of Scz organoids. Single-cell sequencing revealed that Scz progenitors were specifically depleted of neuronal programming factors leading to a remodeling of cell-lineages, altered differentiation trajectories, and distorted cortical cell-type diversity. While Scz organoids were similar in their macromolecular diversity to organoids generated from healthy controls (Ctrls), four GWAS factors (PTN, COMT, PLCL1, and PODXL) and peptide fragments belonging to the POU-domain transcription factor family (e.g., POU3F2/BRN2) were altered. This revealed that Scz organoids principally differed not in their proteomic diversity, but specifically in their total quantity of disease and neurodevelopmental factors at the molecular level. Single-cell sequencing subsequently identified cell-type specific alterations in neuronal programming factors as well as a developmental switch in neurotrophic growth factor expression, indicating that Scz neuropathology can be encoded on a cell-type-by-cell-type basis. Furthermore, single-cell sequencing also specifically replicated the depletion of BRN2 (POU3F2) and PTN in both Scz progenitors and neurons. Subsequently, in two mechanistic rescue experiments we identified that the transcription factor BRN2 and growth factor PTN operate as mechanistic substrates of neurogenesis and cellular survival, respectively, in Scz organoids. Collectively, our work suggests that multiple mechanisms of Scz exist in patient-derived organoids, and that these disparate mechanisms converge upon primordial brain developmental pathways such as neuronal differentiation, survival, and growth factor support, which may amalgamate to elevate intrinsic risk of Scz.
An App knock-in rat model for Alzheimer’s disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments
Authors: Pang Keliang , Jiang Richeng , Zhang Wei , Yang Zhengyi , Li Lin-Lin , Shimozawa Makoto , Tambaro Simone , Mayer Johanna , Zhang Baogui , Li Man , Wang Jiesi , Liu Hang , Yang Ailing , Chen Xi , Liu Jiazheng , Winblad Bengt , Han Hua , Jiang Tianzi , Wang Weiwen , Nilsson Per , Guo Wei , Lu Bai 
Published: November 2021

AbstractA major obstacle in Alzheimer’s disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. TheAppknock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiarAppmutations and humanized Aβ sequence knocked into the ratAppgene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of Aβ plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. ThisAppknock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics.
In-orbit demonstration of an iodine electric propulsion system
Authors: Rafalskyi Dmytro , Martínez Javier Martínez , Habl Lui , Zorzoli Rossi Elena , Proynov Plamen , Boré Antoine , Baret Thomas , Poyet Antoine , Lafleur Trevor , Dudin Stanislav , Aanesland Ane 
Published: November 2021

AbstractPropulsion is a critical subsystem of many spacecraft1–4. For efficient propellant usage, electric propulsion systems based on the electrostatic acceleration of ions formed during electron impact ionization of a gas are particularly attractive5,6. At present, xenon is used almost exclusively as an ionizable propellant for space propulsion2–5. However, xenon is rare, it must be stored under high pressure and commercial production is expensive7–9. Here we demonstrate a propulsion system that uses iodine propellant and we present in-orbit results of this new technology. Diatomic iodine is stored as a solid and sublimated at low temperatures. A plasma is then produced with a radio-frequency inductive antenna, and we show that the ionization efficiency is enhanced compared with xenon. Both atomic and molecular iodine ions are accelerated by high-voltage grids to generate thrust, and a highly collimated beam can be produced with substantial iodine dissociation. The propulsion system has been successfully operated in space onboard a small satellite with manoeuvres confirmed using satellite tracking data. We anticipate that these results will accelerate the adoption of alternative propellants within the space industry and demonstrate the potential of iodine for a wide range of space missions. For example, iodine enables substantial system miniaturization and simplification, which provides small satellites and satellite constellations with new capabilities for deployment, collision avoidance, end-of-life disposal and space exploration10–14.
Cell-type specialization is encoded by specific chromatin topologies
Authors: Winick-Ng Warren , Kukalev Alexander , Harabula Izabela , Zea-Redondo Luna , Szabó Dominik , Meijer Mandy , Serebreni Leonid , Zhang Yingnan , Bianco Simona , Chiariello Andrea M. , Irastorza-Azcarate Ibai , Thieme Christoph J. , Sparks Thomas M. , Carvalho Sílvia , Fiorillo Luca , Musella Francesco , Irani Ehsan , Torlai Triglia Elena , Kolodziejczyk Aleksandra A. , Abentung Andreas , Apostolova Galina , Paul Eleanor J. , Franke Vedran , Kempfer Rieke , Akalin Altuna , Teichmann Sarah A. , Dechant Georg , Ungless Mark A. , Nicodemi Mario , Welch Lonnie , Castelo-Branco Gonçalo , Pombo Ana 
Published: November 2021

AbstractThe three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation ofBdnfaway from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.
Drug-drug interactions in atrial fibrillation patients receiving direct oral anticoagulants
Authors: Lee Ji Yun , Oh Il-Young , Lee Ju-Hyeon , Kim Seok , Cho Jihoon , Park Charg Hyun , Yoo Sooyoung , Bang Soo-Mee 
Published: November 2021

AbstractPolypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA2DS2-VASc score in category 0–1, 49.4% in category 2–3, and 22.4% in category ≥ 4. The CHA2DS2-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22–55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11–16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.
Neural correlates of vocal initiation in the VTA/SNc of juvenile male zebra finches
Authors: Yanagihara Shin , Ikebuchi Maki , Mori Chihiro , Tachibana Ryosuke O. , Okanoya Kazuo 
Published: November 2021

AbstractInitiation and execution of complex learned vocalizations such as human speech and birdsong depend on multiple brain circuits. In songbirds, neurons in the motor cortices and basal ganglia circuitry exhibit preparatory activity before initiation of song, and that activity is thought to play an important role in successful song performance. However, it remains unknown where a start signal for song is represented in the brain and how such a signal would lead to appropriate vocal initiation. To test whether neurons in the midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) show activity related to song initiation, we carried out extracellular recordings of VTA/SNc single units in singing juvenile male zebra finches. We found that a subset of VTA/SNc units exhibit phasic activity precisely time-locked to the onset of the song bout, and that the activity occurred specifically at the beginning of song. These findings suggest that phasic activity in the VTA/SNc represents a start signal that triggers song vocalization.