bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study of the relationship between porosity and surface area of carbonate reservoir rocks
Authors: Mohammadi Milad , Shadizadeh Seyed Reza , Manshad Abbas Khaksar , Mohammadi Amir H.
Published: February 2020

Over the time by increasing global demand for source of energy and decreasing hydrocarbon production from reservoirs, recovery methods have become important. The surface area and porosity are central physical characteristics that highly affect the estimation of original oil and gas in place and understanding the mechanisms incorporating in production. The surface area is the internal surface area per unit of pore volume and determines the amount of space in rocks exposed to injectant during injection operation. The occurrence of fractures system in carbonated reservoirs increases the complexity and decreases the homogeneity; hence, it is difficult to determine the correct surface area of reservoir. Therefore, the existence of a local correlation which relates effective porosity to specific surface area is needed and it can help to estimate effective surface area exposed to chemicals during Enhanced Oil Recovery (EOR) process. In this study, the specific surface area in carbonate reservoir rocks was measured by gas adsorption (nitrogen) method and petro-graphical image analysis. In addition, the effective porosity was determined by a gas porosimeter, followed by plotting specific surface area measured by the Brunauer, Emmett and Teller (BET) method versus specific surface area determined from core scan and calibration curve. According to this calibration curve, a new relationship was developed (with R2 = 0.92) that could give BET data for a known data of core scan. The relationship between porosity and specific surface area was analyzed statistically and a relationship with accuracy of R2 = 0.89 was proposed. This relationship was compared with other models such as Pirson and Kotyakhov. Results show that the latter one is more accurate than other models and is more compatible with experimental data (with R2 = 0.84). The results obtained from the experiment indicate that the specific surface area shows an initial decrease upon increasing of porosity up to 0.2. After this decrease, the curve indicates an increasing trend. Moreover, a novel relationship was developed depending on the specific surface area, porosity and permeability and some constant parameters for carbonate rocks (with R2 = 0.95).
Microbe-induced fluid viscosity variation: field-scale simulation, sensitivity and geological uncertainty
Authors: Ansah Eric O. , Vo Thanh Hung , Sugai Yuichi , Nguele Ronald , Sasaki Kyuro
Published: February 2020

This study is intended to expand the scope of microbial enhanced oil recovery (MEOR) simulation studies from 1D to field scale focussing on fluid viscosity variation and heterogeneity that lacks in most MEOR studies. Hence, we developed a model that incorporates: (1) reservoir simulation of microbe-induced oil viscosity reduction and (2) field-scale simulation and robust geological uncertainty workflow considering the influence of well placement. Sequential Gaussian simulation, co-kriging and artificial neural network were used for the petrophysical modelling prior to field-scale modelling. As per this study, the water viscosity increased from 0.5 to 1.72 cP after the microbe growth and increased biomass/biofilm. Also, we investigated the effect of the various component compositions and reaction frequencies on the oil viscosity and possibly oil recovery. For instance, the fraction of the initial CO2in the oil phase (originally in the reservoir) was varied from 0.000148 to 0.005 to promote the reactions, and more light components were produced. It can be observed that the viscosity of oil reduced considerably after 90 days of MEOR operation from an initial 7.1–7.07 cP and 6.40 cP, respectively. Also, assessing the pre- and post-MEOR oil production rate, we witnessed two main typical MEOR field responses: sweeping effect and radial colonization occurring at the start and tail end of the MEOR process, respectively. MEOR oil recovery factors varied from 28.2 to 44.9% OOIP for the various 200 realizations. Since the well placement was the same for all realizations, the difference in the permeability distribution amongst the realizations affected the microbes’ transport and subsequent interaction with nutrient during injection and transport.
Mixed outcomes from conservation practices on soils and Striga-affected yields of a low-input, rice–maize system in Madagascar
Authors: Rodenburg Jonne , Randrianjafizanaka Meva Tahiry , Büchi Lucie , Dieng Ibnou , Andrianaivo Alain Paul , Ravaomanarivo Lala Harivelo Raveloson , Autfray Patrice
Published: February 2020

On upland soils in tropical Africa, common production constraints of rice and maize on smallholder farms are poor soil fertility—resulting from soil erosion and nutrient depletion—and infestation by witchweeds (Striga spp.). In Madagascar where these crops are often grown in rotation, combining legume cover crops with no-till and crop residue mulching—labelled conservation agriculture (CA)—may address these problems. Previously, it was shown that CA practices contribute to steep reductions in Striga asiatica infection. In the current study, a 4-year field experiment was conducted to test, for the first time, the hypothesis that CA practices also contribute to crop yield and soil improvements under Striga-infested conditions. The conventional mono-crop rice–maize rotation practice, involving seasonal tillage and crop residue removal, was compared to three rice–maize rotation systems following CA practices, each with a different legume cover crop option: (1) two short-cycle annual species, cowpea (Vigna unguiculata) and mucuna (Mucuna pruriens); (2) a long-cycle annual, ricebean (Vigna umbellata); and (3) a perennial, stylosanthes (S. guianensis). Rice yields, as well as yield variability, generally increased by changing from the conventional to a CA practice, and maize yields were variable and low in particular under the CA practices. CA practices significantly reduced soil displacement by rainwater runoff and increased soil nitrogen and pH levels (0–20 cm depth), in particular with stylosanthes as cover crop, but did not result in a significant change in soil organic carbon concentration. Rice yields correlated negatively with Striga asiatica plant numbers in years with moderate infection levels. This is the first study that shows mixed outcomes from CA practices in tropical cereal rotation systems on degraded, Striga-infested soils, and subsequent entry points for system improvements. Suggested improvements include judicious cover crop management, complementary fertilizer applications and selection of competitive, resistant and adapted crop varieties.
Collective Investment: Land, Crypto and Coin Schemes: Regulatory ‘Property’
Authors: Tjio Hans , Hu Ying
Published: February 2020

The UK Supreme Court held inAsset Land Plc v. FCA[2016] UKSC 17 that the land-banking scheme required authorization as a collective investment scheme in order to be sold to retail investors. This article critically analyses that decision in light of various approaches to regulating real estate investment trusts (‘REITs’) in the UK, Singapore, and Hong Kong, respectively. It considers the degree to which deference should be given to the views of the regulators, and the ramifications for other areas like initial coin offerings which regulators are increasingly seeing as securities requiring both prospectus disclosure for the token offering and intermediary regulation for its trading. It argues that the regulation of token offerings is both necessary and desirable. Regulation not only helps protect investors from fraudulent token issuers but also helps to fulfil other worthwhile goals, such as providing additional funding for small to medium-sized enterprises and financial inclusion.
A Molecular Foaming and Activation Strategy to Porous N-Doped Carbon Foams for Supercapacitors and CO2 Capture
Authors: Zhou Mengyuan , Lin Yaqian , Xia Huayao , Wei Xiangru , Yao Yan , Wang Xiaoning , Wu Zhangxiong
Published: February 2020

Hierarchically porous carbon materials are promising for energy storage, separation and catalysis. It is desirable but fairly challenging to simultaneously create ultrahigh surface areas, large pore volumes and high N contents in these materials. Herein, we demonstrate a facile acid–base enabled in situ molecular foaming and activation strategy for the synthesis of hierarchically macro-/meso-/microporous N-doped carbon foams (HPNCFs). The key design for the synthesis is the selection of histidine (His) and potassium bicarbonate (PBC) to allow the formation of 3D foam structures by in situ foaming, the PBC/His acid–base reaction to enable a molecular mixing and subsequent a uniform chemical activation, and the stable imidazole moiety in His to sustain high N contents after carbonization. The formation mechanism of the HPNCFs is studied in detail. The prepared HPNCFs possess 3D macroporous frameworks with thin well-graphitized carbon walls, ultrahigh surface areas (up to 3200 m2 g−1), large pore volumes (up to 2.0 cm3 g−1), high micropore volumes (up to 0.67 cm3 g−1), narrowly distributed micropores and mesopores and high N contents (up to 14.6 wt%) with pyrrolic N as the predominant N site. The HPNCFs are promising for supercapacitors with high specific capacitances (185–240 F g−1), good rate capability and excellent stability. They are also excellent for CO2 capture with a high adsorption capacity (~ 4.13 mmol g−1), a large isosteric heat of adsorption (26.5 kJ mol−1) and an excellent CO2/N2 selectivity (~ 24).
Draft whole-genome sequence of Brevibacterium casei strain isolated from a bloodstream infection
Authors: Olender Alina , Rutyna Paweł , Niemcewicz Marcin , Bogut Agnieszka , Ciesielka Marzanna , Teresiński Grzegorz
Published: February 2020

Despite its low virulence potential and a commensal lifestyle as a member of the human skin microbiota, Brevibacterium casei has been increasingly reported as an opportunistic pathogen, especially in immunocompromised patients. Here, we present the draft genome sequence of the S51 strain isolated from a bloodstream infection. To the best of the authors’ knowledge, this is the first report of the draft genome sequence of the B. casei strain isolated from the clinical infection. The strain was identified using phenotypic and molecular methods and subsequently sequenced using the next-generation sequencing. The draft whole genome was assembled de novo, automatically annotated by Rapid Annotations using Subsystems Technology (RAST) server and scrutinized to predict the presence of virulence, resistance, and stress response proteins. The genome size of the S51 strain was 3,743,532 bp and an average G+C content was 68.3%. The predicted genes included 48 genes involved in resistance to antibiotics (including vancomycin, fluoroquinolones, and beta-lactams) and toxic compounds (heavy metals), 16 genes involved in invasion and intracellular resistance (Mycobacterium virulence operons), and 94 genes involved in stress response (osmotic, oxidative stress, cold and heat shock). ResFinder has indicated the presence of a beta-lactamase, and a phenotypic analysis showed resistance to penicillin. This whole-genome NGS project for the S51strain has been deposited at EMBL/GenBank under the accession no. QNGF00000000.
Addressing cyber security skills: the spectrum, not the silo
Authors: Furnell Steven , Bishop Matt
Published: February 2020

With cyber security gaining ever-greater recognition as a key concern in today's organisations, there is an accompanying appreciation that specialist skills are required to support it. However, this has created challenges for employers in recruiting the associated talent, not least because skilled staff are in short supply.

With cyber security becoming a key concern in today's organisations, there is an accompanying appreciation that specialist skills are required to support it.

As Steven Furnell of the University of Plymouth and Matt Bishop of the University of California at Davis explain, it is important to recognise the breadth of skills needed. The natural way to do this is to recruit talent with suitable qualifications, but for this to work we need to understand what they cover and whether they match what organisations need.
The business benefits of cyber security for SMEs
Authors: Lloyd Guy
Published: February 2020

Cyber security is often discussed in terms of data breaches, regulatory fines and business disruption. The advantages are seldom highlighted. For example, effective cyber security makes it possible for companies to innovate and this drives revenue, profit and growth. Defending against cybercrime can deliver genuine benefits for small and medium-size enterprises (SMEs) and result in more valuable organisations.

Cyber security is often discussed in terms of data breaches, regulatory fines and business disruption. However, the advantages are seldom highlighted.

Effective cyber security makes it possible for companies to innovate and this drives revenue, profit and growth. Defending against cybercrime can deliver genuine benefits for small and medium-size enterprises. And as organisations of all sizes move towards driving efficiency through digitising processes, it's important for business leaders to redefine how they think about security, argues Guy Lloyd of CySure.
Rationality, uncertainty, and unanimity: an epistemic critique of contractarianism
Authors: Schaefer Alexander
Published: February 2020

This paper considers contractarianism as a method of justification. The analysis accepts the key tenets of contractarianism: expected utility maximization, unanimity as the criteria of acceptance, and social-scientific uncertainty of modelled agents. In addition to these three features, however, the analysis introduces a fourth feature: a criteria of rational belief formation, viz. Bayesian belief updating. Using a formal model, this paper identifies a decisive objection to contractarian justification. Insofar as contractarian projects approximate the Agreement Model, therefore, they fail to justify their conclusions. Insofar as they fail to approximate the Agreement Model, they must explain which modelling assumption they reject.
The effects of pre-task planning on EFL learners’ oral performance in a 3D multi-user virtual environment
Authors: Chen Julian ChengChiang
Published: February 2020

Prior research on pre-task planning examines its effects on the quality of second language (L2) learners’ planned output. Planning mitigates the cognitive overload placed upon L2 learners’ oral performance, thus improving language production. Despite the pedagogical benefits, studies on pre-task planning on L2 learners’ oral output are conducted mostly in a lab or class setting. Whether or not similar effects of pre-task planning can be evidenced in three-dimensional (3D) multi-user virtual environments (MUVEs), such as Second Life (SL), is still less explored. Hence, this study investigates whether pre-task planning could enhance the quality and quantity of English as a foreign language (EFL) learners’ task-oriented, voice-based outcomes in SL. Nine EFL learners worldwide participated in this 10-session virtual class. Data were collected through students’ oral presentations in performing real-life simulated tasks related to their home cultures and interests. Yuan and Ellis’s (2003) framework of T-units measures was adopted to analyze their linguistic performance measured by complexity and accuracy. Results indicated that EFL learners showed statistically significant improvement on grammatical complexity on the levels of syntactic complexity and variety (but not on lexical variety) and on linguistic accuracy across all measured levels (error-free clauses/T-units/verb forms). It is suggested that pre-task planning can be seeded in task-based instruction either in a classroom-based or 3D MUVE setting to optimize the quality of learners’ linguistic performance. Tasks that are real-world oriented and targeting learners’ cultural repertoires and world knowledge also positively impact their virtual learning experiences. These significant implications add new research and pedagogical dimensions to the field of computer-assisted language learning.
Quality of life assessment in children before and after a successful ablation for supraventricular tachycardia
Authors: Gonzalez Corcia M Cecilia , Peters Laura , Sluysmans Thierry , Moniotte Stephane , Carbonez Karlien , Barrea Catherine , Vo Christophe , Vanhoutte Laetitia , Scavee Christophe
Published: February 2020

Background and Objectives:

Young patients suffering from rhythm disorders have a negative impact in their quality of life. In recent years, ablation has become the first-line therapy for supraventricular arrhythmias in children. In the light of the current expertise and advancement in the field, we decided to evaluate the quality of life in young patients with supraventricular arrhythmias before and after a percutaneous ablation procedure.

Methods:

The prospective cohort consisted of patients <18 years with structurally normal hearts and non-pre-excited supraventricular arrhythmias, who had an ablation in our centre from 2013 to 2018. The cohort was evaluated with the PedsQL™ 4.0 Generic Core Scales self-questionnaire prior to and post-ablation.

Results:

The final cohort included 88 patients consisted of 52 males (59%), with a mean age at ablation of 12.5 ± 3.3 years. Forty-two patients (48%) had a retrograde-only accessory pathway mediating the tachycardia, 38 (43%) had atrio-ventricular nodal re-entrant tachycardia, 7 (8%) had ectopic atrial tachycardia, and 1 (1%) had atrial flutter. The main reason for an ablation was the patient’s choice in 53%. There were no severe complications. Comparison between the baseline and post-ablation assessments showed that patients reported significant improvement in the scores for physical health, emotional and social functioning, as well as in the total scores.

Conclusions:

The present study demonstrates that the successful treatment of supraventricular arrhythmias by means of an ablation results in a significant improvement in the quality of self-reported life scores in young patients.
Domain-general inhibition ability predicts the intensity of inhibition on non-target language in bilingual word production: An ERP study
Authors: Kang Chunyan , Ma Fengyang , Li Shuhua , Kroll Judith F. , Guo Taomei
Published: February 2020

This study investigated the predictive effects of executive functions on bilingual language control processes. We used a flanker task, a switching task and an n-back task to investigate inhibition, shifting, and updating, respectively. We adopted a cued language switching task to investigate the language control processes during bilingual word production. Results of linear mixed effects models showed that picture naming in switch trials was significantly slower and elicited larger stimulus-locked N2 and N400-like components. The results further showed that the flanker effect alone robustly predicted the variability of the N2 but not N400-like switch effects. These findings suggest that domain-general inhibition appears to predict the intensity of inhibition exerted on the lexical items in the non-target language during bilingual word production, but bilingual language control only partially overlaps with executive functions.
Constraining Interseismic Deformation of the Cascadia Subduction Zone: New Insights From Estimates of Vertical Land Motion Over Different Timescales
Authors: Yousefi Maryam , Milne Glenn , Li Shaoyang , Wang Kelin , Bartholet Alan
Published: February 2020

We determine late Holocene (past 4 kyr) vertical land motion (VLM) rates from relative sea level observations along the coastline of western North America and compare these to contemporary (decadal‐scale) rates inferred from Global Positioning System data. The residual rates (contemporary minus late Holocene) indicate uplift at most locations, which likely reflects short‐term signals associated with the Cascadia subduction earthquake cycle and processes that were recently activated. Regarding the latter, we model and remove the signals associated with ground water extraction and twentieth‐century glacier retreat, which have a significant influence in, respectively, California and southern British Columbia. We interpret the remaining signal as being dominated by interseismic deformation associated with the locking of the Cascadia megathrust. A preliminary comparison of this signal with output from a model of interseismic deformation indicates good agreement at most locations within a range of key model parameter values. This agreement is particularly encouraging as the locking model is based on the inversion of only horizontal land motion observations. Considering the data‐model fit at all locations, preference was found for models featuring nearly full locking to a relatively shallow depth (<30 km), although the locking state preference is variable along the coast and not strong. The best fitting parameter set varies considerably from site to site, and no set of parameter values was able to capture the residual VLM rates in northwestern Vancouver Island. Our study indicates that the residual VLM data provide useful constraints for megathrust locking models of Cascadia subduction.
Wave‐Driven Mean Flow Dynamics in Submerged Canopies
Authors: van Rooijen Arnold , Lowe Ryan , Rijnsdorp Dirk P. , Ghisalberti Marco , Jacobsen Niels G. , McCall Robert
Published: February 2020

The physical roughness (canopies) formed by organisms within aquatic ecosystems (e.g., seagrass, kelp, and mangroves) modifies the local wave‐driven hydrodynamics within coastal and estuarine regions. In wave‐dominated environments, an understanding of the mean wave‐driven flows generated within and above canopies is important, as it governs material transport (e.g., of nutrients, sediment, and biota). However, until recently the effect of submerged canopies on wave‐current interactions and the resulting mean (wave‐averaged) flow dynamics has received relatively little attention. In this study, a combination of wave flume experiments and numerical modeling is used to investigate the wave‐induced mean flow profiles in the presence of a submerged canopy. The measured velocities and vegetation forces were used to derive bulk drag and inertia coefficients, and to validate a nonhydrostatic 2DV wave‐flow model. The numerical model results were used to conduct an in‐depth analysis of the mean horizontal momentum terms responsible for driving the mean (horizontal) flow within and above the submerged canopies. We show that the mean canopy hydrodynamics are driven by vertical gradients in wave and turbulent Reynolds stresses, balanced by the mean canopy drag forces. The wave Reynolds stress gradient is the dominant force driving the in‐canopy mean flow and is directly related to the vorticity that is generated when the wave orbital motions become rotational near the canopy interface. This study provides new insight in the mechanisms responsible for wave‐driven mean flows within submerged canopies and guidance for how these hydrodynamics can be predicted in coastal wave‐circulation models.
Buffered, Incomplete, and Shredded: The Challenges of Reading an Imperfect Stratigraphic Record
Authors: Straub Kyle M. , Duller Robert A. , Foreman Brady Z. , Hajek Elizabeth A.
Published: February 2020

Climate, tectonics, and life influence the flux and caliber of sediment transported across Earth's surface. These environmental conditions can leave behind imprints in the Earth's sedimentary archive, but signals of climate, tectonic, and biologic change are not always present in the stratigraphic record. Deterministic and stochastic surface dynamics collectively act as a stratigraphic filter, impeding the burial and preservation of environmental signals in sedimentary deposits. Such impediments form a central challenge to accurately reconstructing environmental conditions through Earth's history. Emergent and self‐organized length and timescales in landscapes, which are themselves influenced by regional environmental conditions, define spatial and temporal sedimentation patterns in basins and fundamentally control the likelihood of environmental signal preservation in sedimentary deposits. Properly characterizing these scales provides a key avenue for incorporating the known “imperfections” of the stratigraphic record into paleoenvironmental reconstructions. These insights are necessary for answering both basic and applied science questions, including our ability to reconstruct the Earth system response to prior episodes of climate, tectonic, or land cover change.
Machine Learning for Stochastic Parameterization: Generative Adversarial Networks in the Lorenz '96 Model
Authors: Gagne David John , Christensen Hannah M. , Subramanian Aneesh C. , Monahan Adam H.
Published: February 2020

Stochastic parameterizations account for uncertainty in the representation of unresolved subgrid processes by sampling from the distribution of possible subgrid forcings. Some existing stochastic parameterizations utilize data‐driven approaches to characterize uncertainty, but these approaches require significant structural assumptions that can limit their scalability. Machine learning models, including neural networks, are able to represent a wide range of distributions and build optimized mappings between a large number of inputs and subgrid forcings. Recent research on machine learning parameterizations has focused only on deterministic parameterizations. In this study, we develop a stochastic parameterization using the generative adversarial network (GAN) machine learning framework. The GAN stochastic parameterization is trained and evaluated on output from the Lorenz '96 model, which is a common baseline model for evaluating both parameterization and data assimilation techniques. We evaluate different ways of characterizing the input noise for the model and perform model runs with the GAN parameterization at weather and climate time scales. Some of the GAN configurations perform better than a baseline bespoke parameterization at both time scales, and the networks closely reproduce the spatiotemporal correlations and regimes of the Lorenz '96 system. We also find that, in general, those models which produce skillful forecasts are also associated with the best climate simulations.
Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety
Authors: Balderston Nicholas L. , Beydler Emily M. , Goodwin Madeline , Deng Zhi-De , Radman Thomas , Luber Bruce , Lisanby Sarah H. , Ernst Monique , Grillon Christian
Published: February 2020

Anxiety disorders are the most prevalent mental disorders, with few effective neuropharmacological treatments, making treatments development critical. While noninvasive neuromodulation can successfully treat depression, few treatment targets have been identified specifically for anxiety disorders. Previously, we showed that shock threat increases excitability and connectivity of the intraparietal sulcus (IPS). Here we tested the hypothesis that inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting this region would reduce induced anxiety. Subjects were exposed to neutral, predictable, and unpredictable shock threat, while receiving double-blinded, 1 Hz active or sham IPS rTMS. We used global brain connectivity and electric-field modelling to define the single-subject targets. We assessed subjective anxiety with online ratings and physiological arousal with the startle reflex. Startle stimuli (103 dB white noise) probed fear and anxiety during the predictable (fear-potentiated startle, FPS) and unpredictable (anxiety-potentiated startle, APS) conditions. Active rTMS reduced both FPS and APS relative to both the sham and no stimulation conditions. However, the online anxiety ratings showed no difference between the stimulation conditions. These results were not dependent on the laterality of the stimulation, or the subjects’ perception of the stimulation (i.e. active vs. sham). Results suggest that reducing IPS excitability during shock threat is sufficient to reduce physiological arousal related to both fear and anxiety, and are consistent with our previous research showing hyperexcitability in this region during threat. By extension, these results suggest that 1 Hz parietal stimulation may be an effective treatment for clinical anxiety, warranting future work in anxiety patients.
Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop
Authors: Chen Fan , Jiang Guowei , Liu Hui , Li Zemin , Pei Yuxin , Wang Hua , Pan Hehai , Cui Haowen , Long Jun , Wang Jianru , Zheng Zhaomin
Published: February 2020

The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin (IL)-1β, and is one of the main causes of intervertebral disc degeneration (IVDD). NLR pyrin domain containing 3 (NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model; moreover, NLRP3 inflammasome activation (NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus (NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species (mtROS) production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mtROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.
Integrating DNA methylation measures to improve clinical risk assessment: are we there yet? The case of BRCA1 methylation marks to improve clinical risk assessment of breast cancer
Authors: Wong Ee Ming , Southey Melissa C. , Terry Mary Beth
Published: February 2020

Current risk prediction models estimate the probability of developing breast cancer over a defined period based on information such as family history, non-genetic breast cancer risk factors, genetic information from high and moderate risk breast cancer susceptibility genes and, over the past several years, polygenic risk scores (PRS) from more than 300 common variants. The inclusion of additional data such as PRS improves risk stratification, but it is anticipated that the inclusion of epigenetic marks could further improve model performance accuracy. Here, we present the case for including information on DNA methylation marks to improve the accuracy of these risk prediction models, and consider how this approach contrasts genetic information, as identifying DNA methylation marks associated with breast cancer risk differs inherently according to the source of DNA, approaches to the measurement of DNA methylation, and the timing of measurement. We highlight several DNA-methylation-specific challenges that should be considered when incorporating information on DNA methylation marks into risk prediction models, using BRCA1, a highly penetrant breast cancer susceptibility gene, as an example. Only after careful consideration of study design and DNA methylation measurement will prospective performance of the incorporation of information regarding DNA methylation marks into risk prediction models be valid.
NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis
Authors: Liu Hui , Zhu Yuanli , Gao Yutong , Qi Dahu , Zhao Liming , Zhao Libo , Liu Changyu , Tao Tenghui , Zhou Chuankun , Sun Xuying , Guo Fengjing , Xiao Jun
Published: February 2020

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor and plays a vital role in inflammatory reactions. However, whether NR1D1 is involved in synovial inflammation and joint destruction during the pathogenesis of RA is unknown. In this study, we found that NR1D1 expression was increased in synovial tissues from patients with RA and decreased in RA Fibroblast-like synoviocytes (FLSs) stimulated with IL-1β in vitro. We showed that NR1D1 activation decreased the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs), while NR1D1 silencing exerted the opposite effect. Furthermore, NR1D1 activation reduced reactive oxygen species (ROS) generation and increased the production of nuclear transcription factor E2-related factor 2 (Nrf2)-associated enzymes. Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways were blocked by the NR1D1 agonist SR9009 but activated by NR1D1 silencing. NR1D1 activation also inhibited M1 macrophage polarization and suppressed osteoclastogenesis and osteoclast-related genes expression. Treatment with NR1D1 agonist SR9009 in collagen-induced arthritis (CIA) mouse significantly suppressed the hyperplasia of synovial, infiltration of inflammatory cell and destruction of cartilage and bone. Our findings demonstrate an important role for NR1D1 in RA and suggest its therapeutic potential.
Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson’s disease models
Authors: Zhuang Xu-Xu , Wang Sheng-Fang , Tan Yuan , Song Ju-Xian , Zhu Zhou , Wang Zi-Ying , Wu Ming-Yue , Cai Cui-Zan , Huang Zhi-Jian , Tan Jie-Qiong , Su Huan-Xing , Li Min , Lu Jia-Hong
Published: February 2020

Autophagy, a conserved cellular degradation and recycling process, can be enhanced by nutrient depletion, oxidative stress or other harmful conditions to maintain cell survival. 6-Hydroxydopamine/ascorbic acid (6-OHDA/AA) is commonly used to induce experimental Parkinson’s disease (PD) lesions by causing oxidative damage to dopaminergic neurons. Activation of autophagy has been observed in the 6-OHDA-induced PD models. However, the mechanism and exact role of autophagy activation in 6-OHDA PD model remain inconclusive. In this study, we report that autophagy was triggered via mucolipin 1/calcium/calcineurin/TFEB (transcription factor EB) pathway upon oxidative stress induced by 6-OHDA/AA. Interestingly, overexpression of TFEB alleviated 6-OHDA/AA toxicity. Moreover, autophagy enhancers, Torin1 (an mTOR-dependent TFEB/autophagy enhancer) and curcumin analog C1 (a TFEB-dependent and mTOR-independent autophagy enhancer), significantly rescued 6-OHDA/AA-induced cell death in SH-SY5Y cells, iPSC-derived DA neurons and mice nigral DA neurons. The behavioral abnormality of 6-OHDA/AA-treated mice can also be rescued by Torin 1 or C1 administration. The protective effects of Torin 1 and C1 can be blocked by autophagy inhibitors like chloroquine (CQ) or by knocking down autophagy-related genes TFEB and ATG5. Taken together, this study supports that TFEB-mediated autophagy is a survival mechanism during oxidative stress and pharmacological enhancement of this process is a neuroprotective strategy against oxidative stress-associated PD lesions.
Silencing lncRNA Lfar1 alleviates the classical activation and pyoptosis of macrophage in hepatic fibrosis
Authors: Zhang Kun , Shi Zhemin , Zhang Mengxia , Dong Xueyi , Zheng Lina , Li Guantong , Han Xiaohui , Yao Zhi , Han Tao , Hong Wei
Published: February 2020

Hepatic fibrosis is a common pathological consequence of a sustained wound healing response to continuous liver injury, characterized by increased production and accumulation of extracellular matrix. If unresolved, the fibrotic process results in organ failure, and eventually death after the development of cirrhosis. It has been suggested that macrophages play central role in the progression of hepatic fibrosis, which is related to inflammation and pyroptosis, a novel programmed and proinflammatory cell death. However, it remains far less clear if, or how, lncRNAs regulates the activation and pyroptosis of macrophage in hepatic fibrosis. In the present study, we demonstrated that the liver-enriched lncRNA Lfar1, which has been reported to promote hepatic fibrosis through inducing hepatic stellate cells activation and hepatocytes apoptosis, was dysregulated during proinflammatory M1 activation and pyroptosis of macrophage. Our study revealed that silencing lnc-Lfar1 by a lentivirus-shRNA alleviated CCl4- and BDL-induced proinflammatory M1 macrophage activation and NLRP3 inflammasome-mediated pyroptosis. Furthermore, the in vitro experiments demonstrated that lnc-Lfar1 knockdown significantly suppressed LPS- and IFN-γ-induced proinflammatory activation of macrophages, and inhibited LPS/ATP- and LPS/Nigericin-induced NLRP3 inflammasome-mediated pyroptosis. Mechanistically, lnc-Lfar1 regulated LPS- and IFN-γ-induced proinflammatory activation of macrophages through the NF-ĸB pathway. All these data supported our conclusion that lnc-Lfar1 plays a vital role in controlling the activation and pyroptosis of macrophage, thus providing a possible therapeutic target against inflammation-related disorders including hepatic fibrosis.
Nutritional intervention with cyanidin hinders the progression of muscular dystrophy
Authors: Saclier Marielle , Bonfanti Chiara , Antonini Stefania , Angelini Giuseppe , Mura Giada , Zanaglio Federica , Taglietti Valentina , Romanello Vanina , Sandri Marco , Tonelli Chiara , Petroni Katia , Cassano Marco , Messina Graziella
Published: February 2020

Muscular Dystrophies are severe genetic diseases due to mutations in structural genes, characterized by progressive muscle wasting that compromises patients’ mobility and respiratory functions. Literature underlined oxidative stress and inflammation as key drivers of these pathologies. Interestingly among different myofiber classes, type I fibers display a milder dystrophic phenotype showing increased oxidative metabolism. This work shows the benefits of a cyanidin-enriched diet, that promotes muscle fiber-type switch and reduced inflammation in dystrophic alpha-sarcoglyan (Sgca) null mice having, as a net outcome, morphological and functional rescue. Notably, this benefit is achieved also when the diet is administered in dystrophic animals when the signs of the disease are seriously evident. Our work provides compelling evidence that a cyanidin-rich diet strongly delays the progression of muscular dystrophies, paving the way for a combinatorial approach where nutritional-based reduction of muscle inflammation and oxidative stress facilitate the successful perspectives of definitive treatments.
Turning main-group element magnesium into a highly active electrocatalyst for oxygen reduction reaction
Authors: Liu Shuai , Li Zedong , Wang Changlai , Tao Weiwei , Huang Minxue , Zuo Ming , Yang Yang , Yang Kang , Zhang Lijuan , Chen Shi , Xu Pengping , Chen Qianwang
Published: February 2020

It is known that the main-group metals and their related materials show poor catalytic activity due to a broadened single resonance derived from the interaction of valence orbitals of adsorbates with the broad sp-band of main-group metals. However, Mg cofactors existing in enzymes are extremely active in biochemical reactions. Our density function theory calculations reveal that the catalytic activity of the main-group metals (Mg, Al and Ca) in oxygen reduction reaction is severely hampered by the tight-bonding of active centers with hydroxyl group intermediate, while the Mg atom coordinated to two nitrogen atoms has the near-optimal adsorption strength with intermediate oxygen species by the rise of p-band center position compared to other coordination environments. We experimentally demonstrate that the atomically dispersed Mg cofactors incorporated within graphene framework exhibits a strikingly high half-wave potential of 910 mV in alkaline media, turning a s/p-band metal into a highly active electrocatalyst.
A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions
Authors: Grossi Elena , Raimondi Ivan , Goñi Enrique , González Jovanna , Marchese Francesco P. , Chapaprieta Vicente , Martín-Subero José I. , Guo Shuling , Huarte Maite
Published: February 2020

LncRNAs have been shown to be direct players in chromatin regulation, but little is known about their role at active genomic loci. We investigate the role of lncRNAs in gene activation by profiling the RNA interactome of SMARCB1-containing SWI/SNF complexes in proliferating and senescent conditions. The isolation of SMARCB1-associated transcripts, together with chromatin profiling, shows prevalent association to active regions where SMARCB1 differentially binds locally transcribed RNAs. We identify SWINGN, a lncRNA interacting with SMARCB1 exclusively in proliferating conditions, exerting a pro-oncogenic role in some tumor types. SWINGN is transcribed from an enhancer and modulates the activation of GAS6 oncogene as part of a topologically organized region, as well as a larger network of pro-oncogenic genes by favoring SMARCB1 binding. Our results indicate that SWINGN influences the ability of the SWI/SNF complexes to drive epigenetic activation of specific promoters, suggesting a SWI/SNF-RNA cooperation to achieve optimal transcriptional activation.
Confined water-mediated high proton conduction in hydrophobic channel of a synthetic nanotube
Authors: Otake Ken-ichi , Otsubo Kazuya , Komatsu Tokutaro , Dekura Shun , Taylor Jared M. , Ikeda Ryuichi , Sugimoto Kunihisa , Fujiwara Akihiko , Chou Chien-Pin , Sakti Aditya Wibawa , Nishimura Yoshifumi , Nakai Hiromi , Kitagawa Hiroshi
Published: February 2020

Water confined within one-dimensional (1D) hydrophobic nanochannels has attracted significant interest due to its unusual structure and dynamic properties. As a representative system, water-filled carbon nanotubes (CNTs) are generally studied, but direct observation of the crystal structure and proton transport is difficult for CNTs due to their poor crystallinity and high electron conduction. Here, we report the direct observation of a unique water-cluster structure and high proton conduction realized in a metal-organic nanotube, [Pt(dach)(bpy)Br]4(SO4)4·32H2O (dach: (1R, 2R)-(–)-1,2-diaminocyclohexane; bpy: 4,4’-bipyridine). In the crystalline state, a hydrogen-bonded ice nanotube composed of water tetramers and octamers is found within the hydrophobic nanochannel. Single-crystal impedance measurements along the channel direction reveal a high proton conduction of 10−2 Scm−1. Moreover, fast proton diffusion and continuous liquid-to-solid transition are confirmed using solid-state 1H-NMR measurements. Our study provides valuable insight into the structural and dynamical properties of confined water within 1D hydrophobic nanochannels.
Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment
Authors: Liu Zhigang , Dai Xiaoshuang , Zhang Hongbo , Shi Renjie , Hui Yan , Jin Xin , Zhang Wentong , Wang Luanfeng , Wang Qianxu , Wang Danna , Wang Jia , Tan Xintong , Ren Bo , Liu Xiaoning , Zhao Tong , Wang Jiamin , Pan Junru , Yuan Tian , Chu Chuanqi , Lan Lei , Yin Fei , Cadenas Enrique , Shi Lin , Zhao Shancen , Liu Xuebo
Published: February 2020

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.
Unveiling contextual realities by microscopically entangling a neutron
Authors: Shen J. , Kuhn S. J. , Dalgliesh R. M. , de Haan V. O. , Geerits N. , Irfan A. A. M. , Li F. , Lu S. , Parnell S. R. , Plomp J. , van Well A. A. , Washington A. , Baxter D. V. , Ortiz G. , Snow W. M. , Pynn R.
Published: February 2020

The development of qualitatively new measurement capabilities is often a prerequisite for critical scientific and technological advances. Here we introduce an unconventional quantum probe, an entangled neutron beam, where individual neutrons can be entangled in spin, trajectory and energy. The spatial separation of trajectories from nanometers to microns and energy differences from peV to neV will enable investigations of microscopic magnetic correlations in systems with strongly entangled phases, such as those believed to emerge in unconventional superconductors. We develop an interferometer to prove entanglement of these distinguishable properties of the neutron beam by observing clear violations of both Clauser-Horne-Shimony-Holt and Mermin contextuality inequalities in the same experimental setup. Our work opens a pathway to a future of entangled neutron scattering in matter.
Electrochemically-stable ligands bridge the photoluminescence-electroluminescence gap of quantum dots
Authors: Pu Chaodan , Dai Xingliang , Shu Yufei , Zhu Meiyi , Deng Yunzhou , Jin Yizheng , Peng Xiaogang
Published: February 2020

Colloidal quantum dots are promising emitters for quantum-dot-based light-emitting-diodes. Though quantum dots have been synthesized with efficient, stable, and high colour-purity photoluminescence, inheriting their superior luminescent properties in light-emitting-diodes remains challenging. This is commonly attributed to unbalanced charge injection and/or interfacial exciton quenching in the devices. Here, a general but previously overlooked degradation channel in light-emitting-diodes, i.e., operando electrochemical reactions of surface ligands with injected charge carriers, is identified. We develop a strategy of applying electrochemically-inert ligands to quantum dots with excellent luminescent properties to bridge their photoluminescence-electroluminescence gap. This material-design principle is general for boosting electroluminescence efficiency and lifetime of the light-emitting-diodes, resulting in record-long operational lifetimes for both red-emitting light-emitting-diodes (T95 > 3800 h at 1000 cd m−2) and blue-emitting light-emitting-diodes (T50 > 10,000 h at 100 cd m−2). Our study provides a critical guideline for the quantum dots to be used in optoelectronic and electronic devices.