bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH PENERAPAN KURIKULUM TERHADAP MOTIVASI DAN MINAT BELAJAR SISWA DENGAN ANGKET SKALI (SKALA LIKERT) PADA MATA PELAJARAN MATEMATIKA DI SMK TRUNOJOYO JEMBER
Authors: Anggraeni Della Putri
Published: May 2021

Abstrak

 

      Pengaruh penerapan kurikulum  terhadap motivasi dan minat belajar siswa dengan angket skali (skala likert) pada mata pelajaran matematika di SMK Trunojoyo Jember, penelitian ini dilatar belakangi kurangnya motivasi dan minat belajar siswa yang ada di SMK Trunojoyo Jember terutama pada kelas IX BDP setelah menerapkan Kurikulum 2013. Penelitian ini bertujuan untuk mengetahuai ada atau tidaknya pengaruh penerapan Kurikulum 2013 terhadap motivasi dan minat belajarsiswa. Penelitian dilakukan di SMK Trunojoyo Jember. Variabel yang digunakan dalam penelitian ini yaitu, Kurikulum 2013(Y), Motivasi Belajar (X1), dan Minat Belajar (X2). Penelitianini termasuk penelitianex post facto dengan jenis penelitian kuantitatif. Dalam penelitian ini penulis menggunakan rancangan penelitian Pendekatan Paradigma Berganda. Berdasarkan hasil analisis data dan pembahasan yang telah diuraikan, maka diperoleh kesimpulannya dengan menggunakan Uji F dengan perhitungan manual, didapatkan nilai Fhitung lebih besar dari nilai Ftabel atau 15,10 > 3,35 yang berarti Ho ditolak, sehingga dapat disimpulkan bahwa ada pengaruh penerapan Kurikulum 2013 terhadap motivasi serta minat belajarsiswa.

Kata Kunci : Kurikulum 2013, Motivasi Belajar, Minat Belajar
Analysis of Organizational Excellence Based on Independent Key Indicators among Hungarian SME Leaders
Authors: Csapai Erzsébet Gyopár , Berke Szilárd
Published: May 2021

Excellence and success are those questions, which could hardly be held or clarified because there are exceptionally subjective and complex correlations behind the definitions. In specific literature we could see that success could be defined in many ways, but there is not any index number or formula that anyone could determine easily and according to that, “label” the companies. The conventional performance/excellence measuring methods are based on the financial indices, but we had a plan to measure other indicators. Therefore, we asked questions about the market share, size of the company, growth rate, export activities, efficiency, and the amount of turnover, awards, prominence lists, years of experience as a leader, quality of abilities as a leader. The number of the incoming questionnaires was 148 from Hungary (CEO-s and leading managers from the highest positions). Our results shows that the chosen variables to measure the organizational excellence as awards and appreciations, export activity, TOP-listing and market influence has impact on organizational excellence, so we can conclude that in the performance measurement systems it is important to include the “non numeric financial” indicators, too. Based on the correlations between the indicators and the organizational excellence we can conclude that in line with the company size, the chance rises to be awarded, the number of employees influences the chance to appear on prominence lists, and also affects the strength of the market position. Regarding the personal leadership we can establish that the micro- and small-sized enterprises have got real backwardness in the field of management in proportion to the multinational companies, and the self-assessment of the leaders is still rather low.
PERSEPSI ORANG TUA TERHADAP PENDIDIKAN ANTI KORUPSI PADA ANAK USIA DINI BERBASIS GADGET
Authors: Saraswati Gaharani , Soleh Mirwan Aji
Published: May 2021

Kasus korupsi dewasa ini telah berkembang dan mengakar di berbagai sendi kehidupan bangsa Indonesia. Indonesia bahkan menjadi salah satu negara yang terkorup di dunia. Transparency International (TI) menyebutkan bahwa Indeks Persepsi Korupsi (IPK) Indonesia mengalami peningkatan dari tahun ke tahun. Melihat kondisi tersebut, diperlukan berbagai upaya pemberantasan korupsi. Salah satunya melalui upaya preventif berupa pendidikan anti korupsi sejak dini. Usia dini (0-8 tahun) merupakan usia emas (golden age). Dengan pendidikan anti korupsi yang diberikan sejak dini diharapkan akan terciptanya generasi muda yang sadar akan bahaya korupsi. Hal yang tidak kalah penting untuk mendukung pendidikan anti korupsi adalah adanya media pembelajaran yang digunakan. Pengembangan media pembelajaran sebaiknya memanfaatkan teknologi yang ada. Di era sekarang teknologi sulit dipisahkan dari kehidupan manusia, begitu pula anak-anak. Banyak anak yang lekat dengan gadget. Untuk mendukung hal tersebut, maka penelitian ini dilakukan untuk mengetahui persepsi orang tua terhadap pentingnya pendidikan anti korupsi pada anak usia dini berbasis gadget. Metode yang digunakan dalam penelitian ini yaitu deskriptif kuantitatif dengan menggunakan instrumen kuesioner (angket) semi terbuka sebanyak lima pertanyaan. Sampel dalam penelitian ini yaitu 100 orang tua yang memiliki anak usia 4 – 8 tahun di Kabupaten Sumedang. Dari hasil survey diketahui bahwa 62% responden menyatakan pernah melihat bentuk tindakan korupsi sederhana yang dilakukan oleh anak. Semua responden (100%) menyatakan bahwa pencegahan tindakan korupsi sejak dini penting untuk dilakukan. Sebanyak 97% responden menyatakan pernah melakukan upaya pencegahan tindakan korupsi sejak dini. Semua responden (100%) setuju bahwa membaca cerita penting bagi anak. Dan 68% responden setuju bahwa gadget bisa dimanfaatkan sebagai media pembelajaran.
PENGARUH PEMAHAMAN NILAI PANCASILA TERHADAP KESADARAN ANTI BULLIYING DI KALANGAN MAHASISWA PGSD
Authors: Mirawati Mira
Published: May 2021

Tujuan penelitian ini untuk mengetahui pengaruh pemahaman nilai Pancasila terhadap kesadaran anti bullying di kalangan mahasiswa PGSD dengan pengambilan data kuesioner yang melibatkan 63  responden sebagai sampel penelitian. Data yang digunakan berupa data primer yang diperolah melalui penyebaran kuesioner. Teknik analisis data yang digunakan  adalah analisis regresi sederhana, koefisien korelasi dan koefisien determinasi. Hasil  penelitian menunjukkan terdapat pengaruh yang positif antara pemahaman nilai Pancasila terhadap kesadaran anti bullying di kalangan mahasiswa PGSD. Pengaruh tersebut dapat dilihat dari persamaan regresi Ŷ = 71,33 – 0,05 X. Besarnya kontribusi pemahamana nilai Pancasila terhadap kesadaran anti bullying di kalangan mahasiswa PGSD ditunjukkan oleh nilai koefisien determinasi r2 sebesar 0,005. Hal ini berarti peningkatan atau penurunan kesadaran anti bullying di kalangan mahasiswa PGSD dipengaruhi oleh pemahaman nilai Pancasila sebesar 0,05% sedangkan sisanya ditentukan oleh variable lain. Temuan penelitian ini menunjukkan bahwa kesadaran anti bullying di kalangan mahasiswa dapat ditingkatkan melalui pemahaman nilai Pancasila.
A Survey of Recent Patents in Engineering Technology for the Screening, Separation and Processing of Eggshell
Authors: Ahmed Tamer A. E. , Younes Manar , Wu Ling , Hincke Maxwell T.
Published: May 2021

The chicken egg is a well-known complete food of human daily consumption which serves as a cost-effective, high-quality nutrient resource. About 30% of table eggs are directed to breaker plants in developed countries, leading to the generation of substantial eggshell (ES) waste, which is increasingly explored for potential value-added applications. The number of patents describing ES-based applications has increased dramatically in recent years. This review provides insight into the most recent patents published between 2015 and 2020, with focus on different engineering technologies for the screening, separation, and processing of ES. Screening technologies include detection of ES surface spots and glossiness, ES cracks, and mechanical properties, along with identification of chicken breed and enumeration of surface bacterial count. Collection and separation technologies describe separation strategies of ES from egg white (EW), egg yolk (EY), liquid egg, eggshell membrane (ESM), hatchlings, and cooked egg. Separation of ES from liquid eggs utilizes gravity, rotational forces, or air pressure. Processing of ES involves washing and sterilization along with cutting, crushing, and pulverization technologies that enable the collection of ES suitable for value-added applications. In addition, ES carving (mechanical and laser) opens up the realm of artwork and decoration. Furthermore, intact ES can be utilized for food serving. The exponential increase in innovative screening, separation, collection, and processing technologies reflects industrial interest to upscale low-value ES waste material, and is a first crucial step in the emergence of advanced technologies that exploit the biomedical, chemical, engineering, and environmental applications for ES.
Accelerating Urban Heating Under Land-Cover and Climate Change Scenarios in Indonesia: Application of the Universal Thermal Climate Index
Authors: Setiawati Martiwi Diah , Jarzebski Marcin Pawel , Gomez-Garcia Martin , Fukushi Kensuke
Published: May 2021

Climate change causing an increase of frequency and magnitude of heat waves has a huge impact on the urban population worldwide. In Indonesia, the Southeast Asian country in the tropical climate zone, the increasing heat wave duration due to climate change will be also magnified by projected rapid urbanization. Therefore, not only climate change mitigation measures but also adaptation solutions to more frequent extreme weather events are necessary. Adaptation is essential at local levels. The projected increase of the heat wave duration will trigger greater health-related risks. It will also drive higher energy demands, particularly in urban areas, for cooling. New smart solutions for growing urbanization for reducing urban heat island phenomenon are critical, but in order to identify them, analyzing the changing magnitude and spatial distribution of urban heat is essential. We projected the current and future spatial variability of heat stress index in three cities in Indonesia, namely, Medan, Surabaya, and Denpasar, under climate change and land-cover change scenarios, and quantified it with the Universal Thermal Climate Index (UTCI) for two periods, baseline (1981–2005) and future (2018–2042). Our results demonstrated that currently the higher level of the UTCI was identified in the urban centers of all three cities, indicating the contribution of urban heat island phenomenon to the higher UTCI. Under climate change scenarios, all three cities will experience increase of the heat, whereas applying the land-cover scenario demonstrated that in only Medan and Denpasar, the UTCI is likely to experience a higher increase by 3.1°C; however, in Surabaya, the UTCI will experience 0.84°C decrease in the period 2018–2042 due to urban greening. This study advanced the UTCI methodology by demonstrating its applicability for urban heat warning systems and for monitoring of the urban green cooling effect, as well as it provides a base for adaptation measures’ planning.
Outdoor Airborne Transmission of Coronavirus Among Apartments in High-Density Cities
Authors: Huang Jianxiang , Jones Phil , Zhang Anqi , Hou Shan Shan , Hang Jian , Spengler John D.
Published: May 2021

The coronaviruses have inflicted health and societal crises in recent decades. Both SARS CoV-1 and 2 are suspected to spread through outdoor routes in high-density cities, infecting residents in apartments on separate floors or in different buildings in many superspreading events, often in the absence of close personal contact. The viability of such mode of transmission is disputed in the research literature, and there is little evidence on the dose–response relationship at the apartment level. This paper describes a study to examine the viability of outdoor airborne transmission between neighboring apartments in high density cities. A first-principles model, airborne transmissionviaoutdoor route (ATOR), was developed to simulate airborne pathogen generation, natural decay, outdoor dispersion, apartment entry, and inhalation exposure of susceptible persons in neighboring apartments. The model was partially evaluated using a smoke tracer experiment in a mock-up high-density city site and cross-checking using the computational fluid dynamics (CFD) models. The ATOR model was used to retrospectively investigate the relationship between viral exposure and disease infection at an apartment level in two superspreading events in Hong Kong: the SARS outbreak in Amoy Gardens and the COVID-19 outbreak in Luk Chuen House. Logistic regression results suggested that the predicted viral exposure was positively correlated with the probability of disease infection at apartment level for both events. Infection risks associated with the outdoor route transmission of SARS can be reduced to <10%, if the quanta emission rate from the primary patient is below 30 q/h. Compared with the indoor route transmission, the outdoor route can better explain patterns of disease infection. A viral plume can spread upward and downward, driven by buoyancy forces, while also dispersing under natural wind. Fan-assistant natural ventilation in residential buildings may increase infection risks. Findings have implication for public health response to current and future pandemics and the ATOR model can serve as planning and design tool to identify the risk of airborne disease transmission in high-density cities.
Accelerated Large-Scale Seismic Damage Simulation With a Bimodal Sampling Approach
Authors: Sheibani Mohamadreza , Ou Ge
Published: May 2021

Regional damage simulation is a promising method to prepare organizations for the unforeseeable impact of a probable seismic natural hazard. Nonlinear time history analysis (NLTHA) of the finite element models (FEM) of the buildings in a region can provide resembling results to the actual buildings’ damages and responses. This approach requires large-scale computational resources, and to improve efficiency, parallel processing and representing building FEM models with lumped mass models are proposed. However, the computing complexity is still far-reaching when high-performance computing is not available. The building inventory of a region consists of numerous similar buildings with a limited number of distinct structures. In this paper, we propose a data-driven method that runs the NLTHA for the distinct structures exclusively and infers the damage and responses of other buildings using a surrogate model. Considering the skewed distribution of the buildings in a region, a novel informative sample selection method is proposed that is designed for bimodal sampling of the input domain. We use the Gaussian process regression as the surrogate model and compare the performance of different sample selection methods. The proposed method is able to approximate the results of the regional damage simulation regarding total economic loss estimation with 98.99% accuracy while reducing the computational demand to about 1/7th of the simulation processing time.
Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation
Authors: Sanavia Tiziana , Huang Chen , Manduchi Elisabetta , Xu Yanwen , Dadi Prasanna K. , Potter Leah A. , Jacobson David A. , Di Camillo Barbara , Magnuson Mark A. , Stoeckert Christian J. , Gu Guoqiang
Published: May 2021

Newly differentiated pancreatic β cells lack proper insulin secretion profiles of mature functional β cells. The global gene expression differences between paired immature and mature β cells have been studied, but the dynamics of transcriptional events, correlating with temporal development of glucose-stimulated insulin secretion (GSIS), remain to be fully defined. This aspect is important to identify which genes and pathways are necessary for β-cell development or for maturation, as defective insulin secretion is linked with diseases such as diabetes. In this study, we assayed through RNA sequencing the global gene expression across six β-cell developmental stages in mice, spanning from β-cell progenitor to mature β cells. A computational pipeline then selected genes differentially expressed with respect to progenitors and clustered them into groups with distinct temporal patterns associated with biological functions and pathways. These patterns were finally correlated with experimental GSIS, calcium influx, and insulin granule formation data. Gene expression temporal profiling revealed the timing of important biological processes across β-cell maturation, such as the deregulation of β-cell developmental pathways and the activation of molecular machineries for vesicle biosynthesis and transport, signal transduction of transmembrane receptors, and glucose-induced Ca2+ influx, which were established over a week before β-cell maturation completes. In particular, β cells developed robust insulin secretion at high glucose several days after birth, coincident with the establishment of glucose-induced calcium influx. Yet the neonatal β cells displayed high basal insulin secretion, which decreased to the low levels found in mature β cells only a week later. Different genes associated with calcium-mediated processes, whose alterations are linked with insulin resistance and deregulation of glucose homeostasis, showed increased expression across β-cell stages, in accordance with the temporal acquisition of proper GSIS. Our temporal gene expression pattern analysis provided a comprehensive database of the underlying molecular components and biological mechanisms driving β-cell maturation at different temporal stages, which are fundamental for better control of the in vitro production of functional β cells from human embryonic stem/induced pluripotent cell for transplantation-based type 1 diabetes therapy.
Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction
Authors: Ermini Leonardo , Farrell Abby , Alahari Sruthi , Ausman Jonathan , Park Chanho , Sallais Julien , Melland-Smith Megan , Porter Tyler , Edson Michael , Nevo Ori , Litvack Michael , Post Martin , Caniggia Isabella
Published: May 2021

Aberrant ceramide build-up in preeclampsia, a serious disorder of pregnancy, causes exuberant autophagy-mediated trophoblast cell death. The significance of ceramide accumulation for lysosomal biogenesis in preeclampsia is unknown. Here we report that lysosome formation is markedly increased in trophoblast cells of early-onset preeclamptic placentae, in particular in syncytiotrophoblasts. This is accompanied by augmented levels of transcription factor EB (TFEB). In vitro and in vivo experiments demonstrate that ceramide increases TFEB expression and nuclear translocation and induces lysosomal formation and exocytosis. Further, we show that TFEB directly regulates the expression of lysosomal sphingomyelin phosphodiesterase (L-SMPD1) that degrades sphingomyelin to ceramide. In early-onset preeclampsia, ceramide-induced lysosomal exocytosis carries L-SMPD1 to the apical membrane of the syncytial epithelium, resulting in ceramide accumulation in lipid rafts and release of active L-SMPD1 via ceramide-enriched exosomes into the maternal circulation. The SMPD1-containing exosomes promote endothelial activation and impair endothelial tubule formation in vitro. Both exosome-induced processes are attenuated by SMPD1 inhibitors. These findings suggest that ceramide-induced lysosomal biogenesis and exocytosis in preeclamptic placentae contributes to maternal endothelial dysfunction, characteristic of this pathology.
Emerging Role of Exosomes in Liquid Biopsy for Monitoring Prostate Cancer Invasion and Metastasis
Authors: Gao Zhengfan , Pang Bairen , Li Jing , Gao Na , Fan Tianli , Li Yong
Published: May 2021

Prostate cancer (PCa) is the most common solid tumor in men. While patients with local PCa have better prognostic survival, patients with metastatic PCa have relatively high mortality rates. Existing diagnostic methods for PCa rely on tissue biopsy and blood prostate-specific antigen (PSA) detection; however, the PSA test does not detect aggressive PCa. Liquid biopsy is a promising technique to overcome tumor heterogeneity in diagnosis, provide more comprehensive information, and track tumor progression over time, allowing for the development of treatment options at all stages of PCa. Exosomes containing proteins and nucleic acids are potential sources of tumor biomarkers. Accumulating evidence indicates that exosomes play important roles in cell communication and tumor progression and are suitable for monitoring PCa progression and metastasis. In this review, we summarize recent advances in the use of exosomal proteins and miRNAs as biomarkers for monitoring PCa invasion and metastasis and discuss their feasibility in clinical diagnosis.
Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor
Authors: Al-Karmalawy Ahmed A. , Dahab Mohammed A. , Metwaly Ahmed M. , Elhady Sameh S. , Elkaeed Eslam B. , Eissa Ibrahim H. , Darwish Khaled M.
Published: May 2021

The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.
Effect of Native Oxide Layer on Mechanochemical Reaction at the GaN–Al2O3 Interface
Authors: Guo Jian , Xiao Chen , Gao Jian , Liu Jinwei , Chen Lei , Qian Linmao
Published: May 2021

Mechanochemical reactions at the gallium nitride-alumina (GaN–Al2O3) interface at nanoscale offer a significant beneficial reference for the high-efficiency and low-destruction ultra-precision machining on GaN surface. Here, the mechanochemical reactions on oxide-free and oxidized GaN surfaces rubbed by the Al2O3 nanoasperity as a function of the ambient humidity were studied. Experimental results reveal that oxidized GaN exhibits a higher mechanochemical removal rate than that of oxide-free GaN over the relative humidity range of 3–80%. The mechanical activation in the mechanochemical reactions at the GaN–Al2O3 interface is well-described by the mechanically-assisted Arrhenius-type kinetics model. The analysis indicates that less external mechanical activation energy is required to initiate the mechanochemical atomic attrition on the oxidized GaN surface compared with the oxide-free GaN surface. These results may not only gain a deep understanding of the mechanochemical removal mechanism of GaN but also provide the basic knowledge for the optimization of the oxidation-assisted ultra-precision machining.
CX3CL1 Recruits NK Cells Into the Central Nervous System and Aggravates Brain Injury of Mice Caused by Angiostrongylus cantonensis Infection
Authors: Zhang Rong , Miao Tingting , Qin Min , Zhao Chengsi , Wang Wei , Zhang Chengcheng , Liu Xinjian , Chen Ying , Chen Ailing , Wang Yong
Published: May 2021

Background

Angiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS.

Methods

Mouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX3CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX3CL1 rat IgG.

Results

The infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX3CL1 in the brain tissue and its receptor CX3CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX3CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection.

Conclusions

Our results demonstrate that the up-regulated CX3CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.
In silico Exploration of Interactions Between Potential COVID-19 Antiviral Treatments and the Pore of the hERG Potassium Channel—A Drug Antitarget
Authors: Al-Moubarak Ehab , Sharifi Mohsen , Hancox Jules C.
Published: May 2021

Background: In the absence of SARS-CoV-2 specific antiviral treatments, various repurposed pharmaceutical approaches are under investigation for the treatment of COVID-19. Antiviral drugs considered for this condition include atazanavir, remdesivir, lopinavir-ritonavir, and favipiravir. Whilst the combination of lopinavir and ritonavir has been previously linked to prolongation of the QTc interval on the ECG and risk of torsades de pointes arrhythmia, less is known in this regard about atazanavir, remdesivir, and favipiravir. Unwanted abnormalities of drug-induced QTc prolongation by diverse drugs are commonly mediated by a single cardiac anti-target, the hERG potassium channel. This computational modeling study was undertaken in order to explore the ability of these five drugs to interact with known determinants of drug binding to the hERG channel pore.

Methods: Atazanavir, remdesivir, ritonavir, lopinavir and favipiravir were docked to in silico models of the pore domain of hERG, derived from cryo-EM structures of hERG and the closely related EAG channel.

Results: Atazanavir was readily accommodated in the open hERG channel pore in proximity to the S6 Y652 and F656 residues, consistent with published experimental data implicating these aromatic residues in atazanavir binding to the channel. Lopinavir, ritonavir, and remdesivir were also accommodated in the open channel, making contacts in a model-dependent fashion with S6 aromatic residues and with residues at the base of the selectivity filter/pore helix. The ability of remdesivir (at 30 μM) to inhibit the channel was confirmed using patch-clamp recording. None of these four drugs could be accommodated in the closed channel structure. Favipiravir, a much smaller molecule, was able to fit within the closed channel and could adopt multiple binding poses in the open channel, but with few simultaneous interactions with key binding residues. Only favipiravir and remdesivir showed the potential to interact with lateral pockets below the selectivity filter of the channel.

Conclusions: All the antiviral drugs studied here can, in principle, interact with components of the hERG potassium channel canonical binding site, but are likely to differ in their ability to access lateral binding pockets. Favipiravir's small size and relatively paucity of simultaneous interactions may confer reduced hERG liability compared to the other drugs. Experimental structure-function studies are now warranted to validate these observations.
MARGIN: Uncovering Deep Neural Networks Using Graph Signal Analysis
Authors: Anirudh Rushil , Thiagarajan Jayaraman J. , Sridhar Rahul , Bremer Peer-Timo
Published: May 2021

Interpretability has emerged as a crucial aspect of building trust in machine learning systems, aimed at providing insights into the working of complex neural networks that are otherwise opaque to a user. There are a plethora of existing solutions addressing various aspects of interpretability ranging from identifying prototypical samples in a dataset to explaining image predictions or explaining mis-classifications. While all of these diverse techniques address seemingly different aspects of interpretability, we hypothesize that a large family of interepretability tasks are variants of the same central problem which is identifying relative change in a model’s prediction. This paper introduces MARGIN, a simple yet general approach to address a large set of interpretability tasks MARGIN exploits ideas rooted in graph signal analysis to determine influential nodes in a graph, which are defined as those nodes that maximally describe a function defined on the graph. By carefully defining task-specific graphs and functions, we demonstrate that MARGIN outperforms existing approaches in a number of disparate interpretability challenges.
Fluid Discrimination in Ultra-Deep Reservoirs Based on a Double Double-Porosity Theory
Authors: Zhou Xinyang , Ba Jing , Santos Juan E. , Carcione José M. , Fu Li-Yun , Pang Mengqiang
Published: May 2021

We develop a methodology, based on rock-physics templates, to effectively identify reservoir fluids in ultra-deep reservoirs, where the poroelasticity model is based on the double double-porosity theory. P-wave attenuation, the ratio of the first Lamé constant to mass density (λ/ρ) and Poisson ratio are used to build the templates at the ultrasonic and seismic frequency bands to quantitatively predict the total and crack (soft) porosities and oil saturation. Attenuation on these frequency bands is estimated with the spectral-ratio and frequency-shift methods. We apply the methodology to fault-controlled karst reservoirs in the Tarim Basin (China), which contain ultra-deep hydrocarbon resources with a diverse pore-crack system, low porosity/permeability and complex oil-water spatial distributions. The results are consistent with well-log data and actual oil recovery. Crack porosity can be used as an indicator to find regions with high oil saturation, since high values implies a good pore connectivity.
Teacher Questions: Mediated-Learning Behaviors Involved in Teacher-Student Interaction During Whole-Class Instruction in Chinese English Classrooms
Authors: Liu Huifang , Gillies Robyn M.
Published: May 2021

Teacher questions have long been considered important in mediating students’ learning in language classrooms. This paper examined the mediated-learning behaviors involved in teacher questions during whole-class instruction in high schools of China. Five lessons of different topics were observed. Conversation analytic approach was applied to analyze teachers’ verbal interactions with students during whole-class teaching. Teachers’ questions and students’ responses were transcribed and categorized as display questions or referential questions. The mediated-learning behaviors involved in the two types of questions were discussed by presenting six sessions of interaction. The study investigated which question type initiated the interaction involving more variety of mediated-learning behaviors and what pedagogical implications this may have for teacher questioning techniques that enhance student learning. The study found the interactions initiated by referential questions contain more varieties of mediated-learning behaviors. This study suggests that teachers need to be encouraged to use referential questions more frequently whether in display interactions or in referential interactions.
Different This Time? The Prospects of CCS in the Netherlands in the 2020s
Authors: Akerboom Sanne , Waldmann Svenja , Mukherjee Agneev , Agaton Casper , Sanders Mark , Kramer Gert Jan
Published: May 2021

Carbon Capture and Sequestration (CCS) has been recognized as an important means of mitigating global climate change, but apart from several pilots, it has not yet been successfully implemented on the large scale needed to live up to the expectations as a mitigation method. In Netherlands, the option of CCS has been the subject of debate for a long time, as three unsuccessful projects – two onshore in Barendrecht and the Northern regions, and one offshore near the Port of Rotterdam – demonstrate. Nevertheless, CCS has been accorded an important place in the current Dutch climate policies, being expected to contribute up to 7 Megaton of CO2 reduction. This is reflected in a fresh crop of CCS project plans. For the most, these plans have a long way to go from the drawing board to actual operations due to the technical, economic, legal and societal challenges ahead. In this article we review the status and possibilities of CCS in Netherlands based on an analysis of existing literature in the relevant disciplines. First, a brief overview of the technology options for carbon capture and storage or utilization is given. This is followed by a detailed analysis of the governmental support for CCS, given the vital role that fit-for-purpose legal frameworks and policy instruments will play in CCS deployment. Technical, legal and policy uncertainties translates into factors inhibiting CCS investment and so the paper then presents a CCS investment project to illustrate how such risks affect the business case for CCS. Finally, bearing in mind that societal acceptance has proved to be a major barrier for CCS, both in Netherlands and elsewhere, the conditions that enhance public acceptance of CCS are examined. Our work shows that while CCS is technically a straightforward proposition, its deployment has historically been hindered by the lack of a sound business case and a compelling and stable socio-technical narrative. The main argument in favor of CCS today is that it offers a transition pathway for rapidly and massively reducing CO2 emissions beyond what could be accomplished by alternative methods like electrification and renewable fuels in near future. The introduction of new financial instruments, increased government support and an improvement in social engagement appear to have enhanced the prospects of CCS in Netherlands, but we feel it is premature to assume that this time everything is different.
Embodied Energy in Export Flows Along Global Value Chain: A Case Study of China’s Export Trade
Authors: Zhang Boya , Bai Shukuan , Ning Yadong
Published: May 2021

Energy issues are closely related to the development of human society and economy. Embodied energy is the total direct and indirect energy consumption required for the production of goods and services. In the context of the intensifying development of economic globalization and prosperity of international trade, embodied energy is considered as a better indicator to comprehensively reflect the nature of a country’s energy use than the direct energy use. The development of trade in value added (TiVA) accounting and global value chain theory has brought new ideas to embodied energy research. This study applies TiVA accounting to the study of embodied energy and establishes a complete framework to decompose the sources, destinations, and transfer routes of embodied energy in a country’s exports, and comprehensively depicts the embodied energy flows in China’s exports at the country and sector levels as an instance. The results show that China exports large amounts of embodied domestic energy use, and export is an important factor for the rapid growth of China’s energy and emissions. At the country level, the United States and EU28 are traditional major importers of China, and developing countries, such as Brazil, India, and Indonesia, are emerging markets. China’s embodied energy flows to different importers vary in terms of trade patterns, flow routes, and the embodied domestic energy intensities. At the sector level, the light industry and the services create more benefits, whereas manufacturing, such as chemicals and metal products, consumes more energy, and there is a mismatch between the main sectors that create economic benefits from exports and the main sectors that consume energy for exports. These results indicate that embodied energy of China’s exports has a great impact on global energy consumption and carbon emission, and the optimizing of China’s export embodied energy structure is conducive to global energy conservation and emission reduction. This article strongly suggests the importance of the global value chain decomposition framework in embodied energy research.
Research on High Quality Evaluation and Influencing Factors of China Energy Finance: Evidence From A-Share New Energy Companies
Authors: Sheng Zeng , Yuan Gao , Xiru Deng , Minglong Zhang , Yi Wu , Yu He
Published: May 2021

High-quality development of energy finance (HQDEF) is not only a key component of high-quality economic development, but also an important solution to the current difficulties of China’s energy industry, such as environmental pollution and supply security. This study first clarifies the connotation and mechanism of high-quality energy finance, and then uses static super-efficiency DEA model as well as dynamic Malmquist index to evaluate the HQDEF from the perspective of input and output. We find that the overall effect of the HQDEF is at a low level. The scale efficiency and technical efficiency are deviating, where the former (latter) continues to expand (decline). The dynamic Malmquist index shows a slight decline in the efficiency of the HQDEF. Further studies on five dimensions of the HQDEF show that innovation has the highest correlation with each new energy industry. Lacking of innovation is the main bottleneck that restricts the development of the current new energy industry. The correlations among different industries have a tendency of “symmetry” and “convergence.” Our study provides countermeasures and suggestions for the high-quality and stable development of China’s energy finance from the perspectives of optimizing the financial support structure, building a technological innovation platform, optimizing the industrial structure, rationally making green investments and open development.
Continuous MYD88 Activation Is Associated With Expansion and Then Transformation of IgM Differentiating Plasma Cells
Authors: Ouk Catherine , Roland Lilian , Gachard Nathalie , Poulain Stéphanie , Oblet Christelle , Rizzo David , Saintamand Alexis , Lemasson Quentin , Carrion Claire , Thomas Morgane , Balabanian Karl , Espéli Marion , Parrens Marie , Soubeyran Isabelle , Boulin Mélanie , Faumont Nathalie , Feuillard Jean , Vincent-Fabert Christelle
Published: May 2021

Activating mutations of MYD88 (MYD88L265P being the far most frequent) are found in most cases of Waldenström macroglobulinemia (WM) as well as in various aggressive B-cell lymphoma entities with features of plasma cell (PC) differentiation, such as activated B-cell type diffuse large B-cell lymphoma (DLBCL). To understand how MYD88 activation exerts its transformation potential, we developed a new mouse model in which the MYD88L252P protein, the murine ortholog of human MYD88L265P, is continuously expressed in CD19 positive B-cells together with the Yellow Fluorescent Protein (Myd88L252P mice). In bone marrow, IgM B and plasma cells were expanded with a CD138 expression continuum from IgMhigh CD138low to IgMlow CD138high cells and the progressive loss of the B220 marker. Serum protein electrophoresis (SPE) longitudinal analysis of 40 Myd88L252P mice (16 to 56 weeks old) demonstrated that ageing was first associated with serum polyclonal hyper gammaglobulinemia (hyper Ig) and followed by a monoclonal immunoglobulin (Ig) peak related to a progressive increase in IgM serum levels. All Myd88L252P mice exhibited spleen enlargement which was directly correlated with the SPE profile and was maximal for monoclonal Ig peaks. Myd88L252P mice exhibited very early increased IgM PC differentiation. Most likely due to an early increase in the Ki67 proliferation index, IgM lymphoplasmacytic (LP) and plasma cells continuously expanded with age being first associated with hyper Ig and then with monoclonal Ig peak. This peak was consistently associated with a spleen LP-like B-cell lymphoma. Clonal expression of both membrane and secreted µ chain isoforms was demonstrated at the mRNA level by high throughput sequencing. The Myd88L252P tumor transcriptomic signature identified both proliferation and canonical NF-κB p65/RelA activation. Comparison with MYD88L265P WM showed that Myd88L252P tumors also shared the typical lymphoplasmacytic transcriptomic signature of WM bone marrow purified tumor B-cells. Altogether these results demonstrate for the first time that continuous MYD88 activation is specifically associated with clonal transformation of differentiating IgM B-cells. Since MYD88L252P targets the IgM PC differentiation continuum, it provides an interesting preclinical model for development of new therapeutic approaches to both WM and aggressive MYD88 associated DLBCLs.
Depth-Dependent Diversity Patterns of Rocky Subtidal Macrobenthic Communities Along a Temperate Fjord in Northern Chilean Patagonia
Authors: Villalobos Vicente I. , Valdivia Nelson , Försterra Günter , Ballyram Stacy , Espinoza Juan Pablo , Wadham Jemma L. , Burgos-Andrade Katherine , Häussermann Vreni
Published: May 2021

Understanding the distribution of biodiversity along environmental gradients allows us to predict how communities respond to natural and anthropogenic impacts. In fjord ecosystems, the overlap of strong salinity and temperature gradients provides us with the opportunity to assess the spatial variation of biodiversity along abiotic environmental gradients. However, in Northern Chilean Patagonia (NCP), a unique and at the same time threatened fjord system, the variation of macrobenthic communities along abiotic environmental gradients is still poorly known. Here, we tested whether macrobenthic species diversity and community structure followed systematic patterns of variation according to the spatial variation in salinity and temperature in Comau Fjord, NCP. A spatially extensive nested sampling design was used to quantify the abundance of subtidal macrobenthic species along the fjord axis (fjord sections: head, middle, and mouth) and a depth gradient (0–21 m). The vertical structure of the water column was strongly stratified at the head of the fjord, characterized by a superficial (depth to ca. 5 m) low-salinity and relatively colder layer that shallowed and decayed toward the mouth of the fjord. The biotic variation followed, in part, this abiotic spatial pattern. Species richness peaked at high salinities (>27 psu) between 5 and 10 m in the head section and between 15 and 21 m in the middle and mouth sections. Diversity and evenness were also highest at these salinities and depth ranges in the head and middle sections, but at shallower depth ranges in the mouth. Information theory-based model selection provided a strong empirical support to the depth- and section-dependent salinity, but not temperature, effects on the three biodiversity metrics. Erect algae and the edible mussel Aulacomya atra numerically dominated in shallow water (0–3 m) at the head and the middle of the fjord, coinciding with the horizontal extension of the low-density water layer—these taxa were further replaced by the crustose algae Lithothamnion sp. and deep-dwelling suspension filters (e.g., corals, polychaetes, and sponges) along depth gradient. Macrobenthic biodiversity correlated, therefore, with the influence of freshwater inputs and the density-driven stratification of the water column in this ecosystem. The spatially variable (across both, horizontal and vertical fjord axes) thresholds observed in our study question the widely accepted pattern of increasing biodiversity with increasing distance from the head of estuarine ecosystems. Finally, non-linear environmental stress models provide us a strong predictive power to understand the responses of these unique ecosystems to natural and anthropogenic environmental changes.
Ocean Surface Flux Algorithm Effects on Earth System Model Energy and Water Cycles
Authors: Reeves Eyre J. E. Jack , Zeng Xubin , Zhang Kai
Published: May 2021

Earth system models parameterize ocean surface fluxes of heat, moisture, and momentum with empirical bulk flux algorithms, which introduce biases and uncertainties into simulations. We investigate the atmosphere and ocean model sensitivity to algorithm choice in the Energy Exascale Earth System Model (E3SM). Flux differences between algorithms are larger in atmosphere simulations (where wind speeds can vary) than ocean simulations (where wind speeds are fixed by forcing data). Surface flux changes lead to global scale changes in the energy and water cycles, notably including ocean heat uptake and global mean precipitation rates. Compared to the control algorithm, both COARE and University of Arizona (UA) algorithms reduce global mean precipitation and top of atmosphere radiative biases. Further, UA may slightly reduce biases in ocean meridional heat transport. We speculate that changes seen here, especially in the ocean, could be even larger in coupled simulations.
Ultrasound Imaging and Antithrombotic Effects of PLA-Combined Fe3O4-GO-ASA Multifunctional Nanobubbles
Authors: Zhang Jie , Liu Zheng , Chang Cunyi , Hu Ming , Teng Yang , Li Jinjing , Zhang Xiangyu , Chi Yanxia
Published: May 2021

PLA-combined ferroferric oxide–graphene oxide–aspirin (Fe3O4-GO-ASA) multifunctional nanobubbles were prepared using the double emulsion-solvent evaporation method. The obtained composite nanobubbles had a regular spherical shape, Zeta potential of (−36.5 ± 10.0) mV, and particle size distribution range of 200–700 nm. The experimental results showed that PLA-combined Fe3O4-GO-ASA nanobubbles could effectively improve the antithrombin parameters of PT, TT, APTT, and INR, and significantly inhibit thrombosis when the composite nanobubbles with a concentration of 80 mg·mL−1 interacted with the rabbit blood. The prepared composite nanobubbles could reach a significant ultrasonic imaging effect and good magnetic targeting under the magnetic field when the nanobubbles' concentration was only 60 mg·mL−1.