bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing the relationship between water pollution and economic activity for a more effective pollution control policy in Bali Province, Indonesia
Authors: Chapagain Saroj Kumar , Mohan Geetha , Rimba Andi Besse , Payus Carolyn , Sudarma I Made , Fukushi Kensuke
Published: July 2021

An adequate water supply is essential for the continued and sustainable growth of the Balinese economy. In addition to mounting water demand, Bali’s water supply has been compromised by high levels of water pollution. Despite being paid great attention, Bali’s earlier efforts to control water pollution yet to prove effective, mainly owing to their reliance on traditional methods and regulations that focus on water pollution being linked to discrete sets of economic activity (e.g., processing industries, livestock farming, and hotels). However, all economic sectors are interconnected through supply chains; thus, water pollution is the combined result of all sectors’ environmental performance. Therefore, determining the structural relationships between water pollution and economic activity serves as an important basis for more effective forms of pollution control for the Balinese economy. In this study, accordingly, we employed an environmentally extended input–output model to establish the links between water pollution and the production processes of the entire economy. Using biochemical oxygen demand (BOD) as a proxy for water quality in our analysis, we estimated that 246,868 tons of BOD were produced from Bali’s economic activity in 2007. Further, we identified the chief BOD-emitting sectors and found that intermediate demand and household demand were the major causes of BOD discharge in the economy. Utilizing supply chain relationships, we also accounted for the indirect role of each sector in total BOD emissions. Moreover, we categorized the sectors into four groups based on their direct and indirect BOD emission characteristics and offered appropriate policy measures for each group. Managing demand (i.e., lowering household consumption and exports) and shifting input suppliers (i.e., from polluters to non-polluters) are effective measures to control pollution for Categories I and II, respectively; clean production and abatement is advised for Category III; and a hybrid approach (i.e., demand management and abatement technology) is recommended for Category IV.
The Topographic Threshold of Gully Erosion and Contributing Factors
Authors: zare maryam , soufi Majid , Nejabat Masoud , Pourghasemi Hamid reza
Published: July 2021

The topographic threshold is based on the power relationship between area and slope and is widely applied in gully-erosion research; however, this relationship requires further testing. Accordingly, the Alamarvdasht Lamerd and Fadagh Larestan regions in Fars Province, Iran, were selected as case studies to explore the topographic threshold for gullies. Thirty active gullies were identified in each study area during field surveys, and data describing land use and land cover, drainage areas, slope, and the physical and chemical properties of the soils were assembled. Multivariate analysis was conducted using SPSS to determine the effects of these factors. Using the power relationship between the catchment area and slope for each gully, the analyses explored critical controls for gully development. The results showed that surface runoff was the most significant effective factor for gullies in the study areas. Sparse ground cover, fine-textured soils, and inappropriate land use all contribute to gully development. The results suggest that the relationship between slope and drainage area in the Fadagh Larestan case study is S = 0.0192 A− 0.159 for gully headcut areas and S = 0.0181 A− 0.258 at gully outlets. The corresponding values of the exponent β at the gully headcuts and outlets at Fadagh were − 0.15, and- 0.25, respectively. The corresponding relationships for gullies in the Alamarvdasht Lamerd area for the gully headcuts and outlets were S = 0.0143 A− 0.061 and S = 0.0073 A− 0. 18, respectively, with β values of -0.06 and − -0.18. This study provides a basis for determining the thresholds for the initiation of gully development. Analyses of the effective factors provide clues to improve the management of bare lands to prevent the initiation of gully erosion.
Sensitivity Enhancement of Silver Based Surface Plasmon Resonance Sensor via Graphene-Dielectric Composite Structure
Authors: Wang Guiqiang , Huang Liang
Published: July 2021

In this paper, a silver based surface plasmon resonance (SPR) sensor with graphene and dielectric layer was presented. The influences of dielectric layer and graphene on sensitivity and other sensing properties were theoretically calculated and then comprehensively discussed. The refractive index sensitivities for composite silver film based SPR sensors with graphene and dielectric layer could be increased by 29% and 288% than that of monolayer silver film based SPR sensor, respectively. Further, the sensitivity could be enhanced by 202% when combining graphene and dielectric layer together. Considering the high adsorptive capacity of graphene for biochemical molecules, the composite silver film with both dielectric layer and graphene would have great potential application in biochemical sensing fields. Further, BSA protein was successfully used to verify the biochemical sensing ability of proposed SPR sensor. The shift of resonance angle is nearly 3.1 folds than that of monolayer silver based SPR sensor.
Inhibiting tumor cell-intrinsic UBA6 by inosine augments tumor immunogenicity
Authors: He Baokun , Zhang Lei , Jiang Li , Yu Liang , Li Qin , Tian Xiangjun , He Jing-Quan , Zeng Ling , Yang Yuqin , Wang Chaoran , Wei Yuhan , Jiang Xiaoyue , Li Jing , Ge Xiaolu , Gu Qisheng , Li Ji-Kun , Wu Di , Sadler Anthony , Yu Di , Xu Dakang , Gao Yue , Yuan Xiangliang
Published: July 2021

Metabolic alteration influences cancer immunity. However, the role and mechanism of metabolic adaption on immune checkpoint blockade (ICB) responses remains ill-defined. Here, to identify metabolites that modulate ICB sensitivity, metabolomic profiling in mouse tumor models and cancer patients treated with ICB was performed. We identified that metabolite inosine was associated with ICB sensitivity in mice and humans, and overcame ICB resistance in several mouse tumor models. Notably, inosine sensitized tumor cells to T cell-mediated cytotoxicity by amplifying tumor-intrinsic immunogenicity. Chemical proteomics further identified that inosine directly bound and inhibited ubiquitin-activating enzyme UBA6. Tumor UBA6 loss augmented tumor immunogenicity and substituted the synergistic effect of inosine in combination with ICB. Clinically, tumor UBA6 expression negatively correlated with ICB response in cancer patients. Thus, we reveal an unappreciated function of inosine on tumor-intrinsic immunogenicity and provide UBA6 as a candidate target for immunotherapy.
Criticality Aware Scheduler Prioritization in Virtual Orthogonal Multichannel Parallelism for 5G Cellular Network
Authors: Ye Dan
Published: July 2021

To fulfill various enhanced requirements of next generation wireless access, 5 G cellular network will drive towards higher energy efficiency, lower latency and higher reliable wireless networks. The key contributions can summarize as follows: (1) proposes frame-based max-weight scheduling (FMWS) with reconfiguration delay in combination of round–robin algorithm can dynamically control throughput and delay. The frame-based dynamic control (FBDC) policy is applicable to 5 G cellular network control systems in data link layer, provides a new framework for developing throughput-optimal network control policies using state-action frequencies. (2) proposes a novel approach in MAC layer--Virtual multichannels Parallelism Carrier Sense Multiple Access (VMCP-CSMA) which can compute a set of TDDM schedules for multiple channels at once rather than computing one schedule at a time and constantly switching or recomputing schedules. (3) proposes a novel criticality aware scheduler prioritization in VMCP-CSMA policy can reorder a set of TDDM schedules based on max-weight scheduling with reconfiguration delay according to different application requirements. It can achieve high throughput and low delay with low complexity compared with other schedulings.
Smart Energy Consumption of IoT With Millimeter-Wave Cognitive Radiofor 5G Cellular Network
Authors: Ye Dan
Published: July 2021

Millimeter-wave technology is rising as a crucial component for 5G radio access and other emerging ancillary wireless networks including Gb/s device-to-device communication and mobile backhaul. This paper envisions that millimeter-wave cognitive radio in 5G network is a proposed smart energy consumption solution of Internet of Things (IoT) devices. Improving resource efficiency and enhancing data rates, resource sharing is a proposed advantage over millimeter wave cognitive radio in 5G IoT network. IoT Fog collaboration is proposed to apply artificial intelligence techniques to offer important energy-saving services allowing integrated systems to perceive, reason, learn, and act intelligently in intelligent gateway control. Smart energy meters are the current energy-saving utility in the flexible deployment of IoT architecture. NarrowBand IoT (NB-IoT) delivers Low Power Wide Area access (LPWA) to a new generation of connected things in the race to 5G IoT network, reducing energy computation and achieving promising network capacity. The renewable energy strategy is a proposed energy-efficiency solution in IoT network, maximizing the power supply while minimizing power consumption. A novel kind of visible light communications (VLC) is proposed to enable mmWave cognitive radio receiver in 5G IoT network. Simulation results show the proposed solution can reap the benefits of higher data rates, more IoT device connectivity, and lower energy consumption.
BIRC5 and PRLR Might Be Novel Immune-Related Prognostic Biomarkers in Adrenocortical Carcinoma (ACC)
Authors: Bai Xiaojie , Yan Xin , Du Guowei , Chen Zhao , Wu Huahui , Tuoheti Kurerban , Liu Tongzu
Published: July 2021

Background: Adrenocortical carcinoma (ACC) is a highly aggressive tumor，which occurs in adrenal cortex. This study aims to identify new immune-related molecular biological markers and therapeutic targets in ACC patients. Results: First, we identified 134 genes by constructing weighted gene co-expression network. Among them, two genes (BIRC5 and PRLR) were eventually regarded as immune-related prognosis biomarkers on the basis of The Immunology Database and Analysis Portal (ImmPort) database. The validation of mRNA level was meaningful (based on Oncomine database and TCGA-ACC). Four methods (overall survival (OS) analysis, disease-free survival (DFS) analysis, stage plot and expression value comparison) were used in GEPIA to verify that PRLR and BIRC5 have significant correlation with the prognosis of ACC. Several other methods including survival analysis, analysis of variance, the spearman correlation analysis, distance correlation analysis and receiver operating characteristic curve were also used for the external validation of them in GEO datasets (GSE10279, GSE19750, GSE76019 and GSE76021). Furthermore, we evaluated the relationship between hub gene expression of and the degree of immune cell infiltration in ACC by ESTIMATE algorithm and ssGSEA. BIRC5 expression was significantly positively related to activated CD4 T cell and type 2 T helper cell. And PRLR expression was positively related to CD56dim NK cell and type 17 T helper cell. Moreover, Gene set enrichment analysis (GSEA) suggested that PRLR has strong correlation with neuroactive ligand receptor interaction and BIRC5 was significantly enriched in cell cycle. In addition, according to Drug Signatures Database (DSigDB), BIRC5 were significantly enriched in “resveratrol_mcf7_down”, “lucanthone_ctd_00006227”, “8-azaguanine_pc3_down”, “thioguanosine _mcf7_down”, “dasatinib_ctd_00004330”, “monobenzone_pc3_down”. Conclusions: In summary, BIRC5 and PRLR were shown to be related to the prognosis of patients with ACC, indicating them as novel immune-related prognostic biomarkers and immunotherapy targets in ACC.
WDR31 is a novel ciliopathy protein displaying functional redundancy with GTPase-activating proteins ELMOD and RP2 in recruiting BBSome to cilium
Authors: Cevik Sebiha , Alabdi Lama , Peng Xiaoyu , Beyer Tina , Zorluer Atiyye , Pir Mustafa , Yenisert Ferhan , Shaheen Ranad , Woerz Franziska , Hoffmann Felix , Altunkaynak Betul , Pir Betul , Boldt Karsten , Karaman Asli , Cakiroglu Miray , Oner Sadik , Cao Ying , Ueffing Marius , Alkuraya Fowzan , Kaplan Oktay
Published: July 2021

The term “ciliopathy” refers to a group of over 35 rare disorders characterized by defective cilia and many overlapping clinical features, such as hydrocephalus, cerebellar vermis hypoplasia, polydactyly, and retinopathy. Even though many genes have been implicated in ciliopathies, the genetic pathogenesis in certain cases remains still undisclosed. Here, we identified a homozygous truncating variant in WDR31 in a patient with a typical ciliopathy phenotype encompassing congenital hydrocephalus, polydactyly, and renal agenesis. WDR31 is an evolutionarily conserved protein that localizes to the cilium and cilia-related compartment. Analysis from zebrafish supports the role of WDR31 in regulating the cilia morphology. The CRISPR/Cas9 knock-in (p.Arg261del) C. elegans model of the patient variant (p.Arg268*) reproduced several cilia-related defects observed in wdr-31 null mutants. Mechanistic analysis from C. elegans revealed that WDR-31 functions redundantly with ELDM-1 (ELMOD protein) and RPI-2 (RP2) to regulate the IFT trafficking through controlling the cilia entry of the BBSome. This work revealed WDR31 as a new ciliopathy protein that regulates IFT and BBSome trafficking.
A Spaced-Repetition Approach to Enhance Medical Student Learning and Engagement in Pharmacology
Authors: Jape Dylan , Zhou Jessie , Bullock Shane
Published: July 2021

Background: Pharmacology is a cornerstone of medical education as it underlies safe prescribing practices. However, medical students have reported unease regarding their perceived proficiency in clinical pharmacology. Despite the significant impetus to improve student outcomes, there is little analysis available of the techniques used by medical students to learn, retain and apply pharmacology knowledge.Methods: A mixed methods, student-focused approach was conducted to design and refine specific resources developed to address gaps in pharmacology education. This methodology comprised an anonymised scoping survey, followed by structured focus group interviews. We developed a relevant and time efficient resource to support long-term revision for academic and clinical success. These resources were released to a cohort of 100 graduate preclinical medical students who were invited at the end of year to evaluate the intervention via a subsequent anonymous survey.Results: The scoping survey received 103 complete responses. Surveys and focus group interviews revealed that only 50% of students engage in ongoing revision. The analysis identified in-semester revision of pharmacology as a significant predictor of strategic and deep learning methods and improved quiz performance (a 5% higher score on average), compared to superficial learning methods. Amongst our cohort, we identified that the evidence-based technique of spaced-repetition was particularly well regarded. Hence, we developed and evaluated a bespoke resource utilising AnkiTM, an open-source, spaced-repetition flashcard program. A total of 1208 flashcards spanning 156 distinct classes of drugs with supplementary summary tables, diagrams and explanatory video and summary guides were created. Designed as a strategic revision tool to reinforce learning, evaluation showed students greatly appreciated the “comprehensive” and “well formatted” AnkiTM resource that supported existing teaching modalities, with a global rating of 3.8 out of 5. Conclusions: Strategic and personalised techniques for pharmacology learning that assist with in-semester revision and long-term retention are highly valued amongst students for examination preparation and preparedness for practice. Collectively, these results define a novel approach to identifying and addressing weaknesses in existing teaching methodologies in a manner that is inclusive of, and acceptable to, medical students.
Observation of the crossover between metallic and insulating regimes of the spin Hall effect
Authors: Moriya Hiroyuki , Musha Akira , Haku Satoshi , Ando Kazuya
Published: July 2021

The physics of the anomalous and spin Hall effects is one of the most intriguing aspects of condensed matter physics. An important finding from a large collection of experimental and theoretical results is the universal scaling of the anomalous or spin Hall conductivity with the electric conductivity. This scaling has been successfully described by the intrinsic Berry curvature and extrinsic scattering mechanisms for metallic systems, revealing the topological nature of these effects. In contrast, the underlying physics in the opposite limit, the disordered insulating regime, is still unclear. In particular, it remains a major challenge to explore the spin Hall effect in the insulating regime. Here, we report the observation of the crossover between the metallic and insulating regimes of the spin Hall effect. The result demonstrates an important correspondence between the spin and anomalous Hall effects, which provides essential information for the fundamental understanding of spin transport.
Pedestrian Evacuation Time Calculation against Tsunami Hazard for Southern Coasts of Bodrum Peninsula
Authors: Çelikbaş Büşra , Tufekci-Enginar Duygu , Dogan Gozde Guney , Kolat Cagil , Santini Marzia , Annunziato Alessandro , Necmioglu Ocal , Yalciner Ahmet Cevdet , Suzen Mehmet Lutfi
Published: July 2021

Historical records with recent events reveal that tsunamis are threatening the western coast of Turkey due to intensely active seismicity of the Eastern Mediterranean Sea. The most recent tsunami events in the region (30 October 2020 Izmir-Samos and 20 July 2017 Bodrum-Kos) restated that the cities located near the Eastern Mediterranean and connected seas should consider tsunami events in their disaster mitigation plans. Bodrum is one of the most critical coastal districts, vulnerable to marine hazards with popular hotels, numerous coastal facilities, long and famous beaches, cultural, historical and touristic places. Tsunami evacuation planning is required for Bodrum district to mitigate the damage caused by destructive tsunami waves inundating on land. In this study, the geospatial distribution of pedestrian evacuation time is calculated based on selected credible worst-case scenarios. A widely used anisotropic least-cost-distance (LCD) model is applied via the Pedestrian Evacuation Analyst Tool (PEAT) to calculate the required time for a pedestrian to evacuate the region under tsunami threat based on the selected scenarios. The model includes landscape properties that affect the walking pace of pedestrians during an evacuation, such as elevation, slope, land cover, and land use types (beach, road, bushes, water bodies, any barriers). The resultant pedestrian evacuation time maps show that the maximum time needed for a pedestrian is 8, 6, 5, 4, 3 minutes for highly populated coastal settlements of Bodrum, which are Central Bodrum, Yahsi, Akyarlar-Karaincir-Aspat Bays, Bitez, and Gumbet Bays, respectively.
FOC-MOP – Fuzzy Optimal Clustering based Multi-Objective Parameter Route Selection for Energy Efficiency
Authors: Sreed Pogula , Venkateswarlu S.
Published: July 2021

Recently, the research area interest towards the development of wireless sensor network (WSN) has increased. However, WSNs have one of significant issues as improving an energy-efficient routing protocol. A WSN has a crucial problem of energy consumption that effects the network lifetime as sensor nodes have a limitation of power. To overcome these limitations, it’s required to improve energy-efficient communication protocols for WSNs. Different types of techniques have considered by various research communities for providing energy-efficient solutions for WSNs. The energy consumption reduces using the clustering as an efficient data collection method and the collected data forward to a cluster-head which belong to the nodes in clustered networks. The information transmits to BS (base station) either in an uncompressed or compressed manner after collecting all data by a cluster-head from all member nodes. Based on other cluster-heads, the data transmit in a multi-hop network. Due to the heavy inter-cluster relay, earlier death happens to the cluster-heads (CHs) that locates very closely to the sink. Therefore, a fuzzy optimal CH selection algorithm has proposed to select the optimal CHs to improve the lifetime. Based on different parameters like cluster load, communication cost, neighbour density, node degree, inter and intra cluster distance, and node energy, the proposed algorithm of CH selection chooses the CHs. To determine an optimal route for transmitting the data from CH to sink, the modified Emperor Penguin Optimization (EPO) uses after selecting the CH. The proposed technique implements and compares with other earlier methods in terms of packet delivery ratio, lifetime, energy consumption, end to end delay and throughput. The proposed approach shows best performance than the other methods based on the simulation results.
Deep learning enables accurate sound redistribution via nonlocal metasurfaces
Authors: Ding Hua , Fang Xinsheng , Jia Bin , Wang Nengyin , CHENG Qian , Li Yong
Published: July 2021

Conventional acoustic metasurfaces are constructed with gradiently "local" phase shift profiles provided by subunits. The local strategy implies the ignorance of the mutual coupling between subunits, which limits the efficiency of targeted sound manipulation, especially in complex environments. By taking into account the "nonlocal" interaction among subunits, nonlocal metasurface offers an opportunity for accurate control of sound propagation, but the requirement of the consideration of gathering coupling among all subunits, not just the nearest-neighbor coupling, greatly increases the complexity of the system and therefore hinders the explorations of functionalities of nonlocal metasurfaces. In this work, empowered by deep learning algorithms, the complex gathering coupling can be learned efficiently from the preset dataset so that the functionalities of nonlocal metasurfaces can be significantly uncovered. As an example, we demonstrate that nonlocal metasurfaces, which can redirect an incident wave into multi-channel reflections with arbitrary energy ratios, can be accurately predicted by deep learning algorithms. Compared to the theory, the relative error of the energy ratios is less than 1\%. Furthermore, experiments witness three-channel reflection with three types of energy ratios of (1, 0, 0), (1/2, 0, 1/2), and (1/3, 1/3, 1/3), proving the validity of the deep learning enabled nonlocal metasurfaces. Our work might blaze a new trail in the design of acoustic functional devices, especially for the cases containing complex wave-matter interactions.
Contamination of the slit-lamp breath shield under face-masking conditions: a prospective clinical study
Authors: Sato Ken-ichi
Published: July 2021

Objective Ophthalmologists have installed breath shields on slit-lamp microscopes to block droplets produced by patients and prevent infection with severe respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 pandemic. This study measured the contamination of one such shield used in clinical practice under face-masking conditions and examined its significance in preventing infection.Methods In this single-center prospective study, measurements were taken at an ophthalmology outpatient unit on 10 weekdays: 5 consultation days and 5 closed days. All patients were required to use face masks, including surgical masks, commercially available cloth masks, and homemade cloth masks. A breath shield, made of polyethylene terephthalate, was hung on the eyepieces of the slit-lamp microscope. Measurement areas of 5 cm2 were set on the patient-side surface of the shield, as well as on the slit-lamp table, where touching was not forbidden. Samples were collected after wiping with 78 vol% ethanol at 9 a.m., at the beginning of office hours. Touching the shield was forbidden during office hours, and the samples were collected again at 5 p.m., at the end of office hours. The total amount of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate was measured as an indicator of the degree of contamination.Results Contamination of the shield had increased by the end of office hours on the consultation days, although the p-value from a paired t-test was slightly above 0.05. In contrast, on days when the department was closed, no difference was observed in the level of contamination between morning and evening. Similarly, the slit-lamp table was significantly contaminated on consultation days, whereas there was no difference in contamination between morning and evening on closed days.Conclusions The results of this study indicate slight contamination of the slit-lamp microscope breath shield by droplets produced by patients who were wearing a face mask.
Discovery of a multi-functional biocatalyst for asymmetric conjugate reduction-reductive amination
Authors: Turner Nicholas , Thorpe Thomas , Marshall James , Harawa Vanessa , Ruscoe Rebecca , Cuetos Anibal , Finnigan James , Angelastro Antonio , Parmeggiani Fabio , Charnock Simon , Howard Roger , Kumar Rajesh , Daniels David , Grogan Gideon
Published: July 2021

A major challenge in chemical synthesis is to develop catalytic systems that convert simple molecules to complex high-value products. Often these valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Of great interest are enantioenriched amine diastereomers, which are prevalent in pharmaceuticals and agrochemicals,1 yet their preparation often relies on low-efficiency multi-step synthesis.2 Herein, we report the discovery and characterisation of a multi-functional biocatalyst, which operates using a previously unreported conjugate reduction-reductive amination mechanism. This enzyme (pIR-120), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates an amine-activated conjugate alkene reduction followed by reductive amination. This enzyme enables the coupling of a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of enantioenriched amine diastereomers. Moreover, employing a racemic substrate partner or conjugated dienyl-ketone provides a means of controlling additional stereocentres using the single catalyst. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by pIR-120 which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.
DNA hyper-methylation associated with schizophrenia may lead to breakdown of self-tolerance
Authors: Wei Hui , Yuan Yanbo , Zhu Caiyun , Ma Mingjie , Yang Fude , Lu Zheng , Wang Chuanyue , Deng Hong , Zhao Jingping , Tian Runhui , Zhu Wanwan , Shen Yan , Yu Xin , Xu Qi
Published: July 2021

Environmental stressors have effects on the genomic DNA methylation patterns of B lymphocytes in schizophrenia (SCZ), which may therefore perturb the immune homeostasis and trigger autoimmune responses. This study aimed to investigate the global genomic DNA methylation differences in remitters of SCZ (RSCZ) and non-remitters of SCZ (NRSCZ), further their effects on autoimmune responses of target genes. A total of 2722 Chinese Han origin subjects were recruited, including a follow-up cohort and a cross-sectional cohort. We found a DMS of cg14341177 in SCZ which inhibit the mRNA alternative splicing of BICD2, further leading to increased plasma anti-BICD2 IgG autoantibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in the endpoint samples of RSCZ, but not in NRSCZ. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and PANSS scores. These data suggest that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.
Bone histology of acipenseriform fishes reveals seasonality during the final years of the Mesozoic.
Authors: Smit Jan , During Melanie , Berruyer Camille , Voeten Dennis , Tafforeau Paul , Sanchez Sophie , Warmerdam Susan Verdegaal , Lubbe Jeroen van der
Published: July 2021

The Cretaceous-Paleogene (KPg) mass extinction ~66 million years ago (Ma) was triggered by the Chicxulub impact on the present-day Yucatán Peninsula. This event caused the extinction of circa 76% of species, including all non-avian dinosaurs, and represents one of the most selective extinctions to date. The timing of the impact and its aftermath have mainly been studied on millennial timescales, leaving the season of the impact unconstrained. Here, we demonstrate that the impact that caused the KPg mass extinction took place during boreal spring. Osteohistology and stable isotope records of exceptionally preserved dermal and perichondrial bones in acipenseriform fishes from the Tanis impact-induced seiche deposits reveal annual cyclicity across the final years of the Cretaceous. These fishes ultimately perished in boreal spring. Annual life cycles, involving seasonal timing and duration of reproduction, feeding, hibernation, and aestivation, vary strongly across latest Cretaceous biotic diversity. We conclude that the timing of the Chicxulub impact in boreal spring significantly influenced selective biotic survival across the KPg boundary.
Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Authors: Zhang Cheng , Liu Heng , Sun Dapeng , Myasnikov Alexander , Damian Marjorie , Baneres Jean-Louis , Sun Ji
Published: July 2021

The 'hunger hormone' ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-Gi signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. The structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable variations of the Gi binding mode are observed in our cryo-EM analysis, indicating the highly dynamic nature of Gi-coupling to GHSR. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs.
Dysfunction of D2 dopamine receptor expressing neurons underlies manic-like behaviors in mice modeling SHANK3 duplication disorder
Authors: Holder Jimmy , Pang Kaifang , Weiwer Michel , Han Kihoon , Wang Wei , Estiphan Theresa , Vuocolo Blake , Jaunarajs Karen , Holson Edward , Lewis Mike , Xu Qihong , Gale Jennifer , Pedersen Steen , Pautler Robia , Standaert David , Wagner Florence , Liu Zhandong , Zoghbi Huda
Published: July 2021

While the contributions of some genes to neuropsychiatric disorders are clear, the downstream neuronal effects are poorly understood. Over-expression of SHANK3, which encodes a key synaptic protein, causes neuropsychiatric phenotypes in humans and manic-like behavior in mice providing an opportunity to interrogate the role of SHANK3 in a subset of neurons that might underlie the manic-like behavior. Herein, we describe Shank3’s critical role in D2 dopamine receptor (D2dr) neurons and show that Shank3 overexpression causes increased synaptic neurotransmission in D2dr, but not D1dr, expressing striatal medium spiny neurons. Either pharmacologic D2dr inhibition or genetic normalization of Shank3 abundance in D2-neurons ameliorates manic-like behaviors. Integrating bioinformatic analyses of Shank3’s striatal interactome, D1 and D2 dopamine receptor binding proteins, and single-cell RNA-seq datasets, we demonstrate a functional relationship between Shank3 and the D2dr—but not the D1dr. Thus, while Shank3 is over-expressed in both D1 and D2 dopamine receptor expressing striatal neurons, D2 neuronal dysfunction causes manic-like behaviors.
Detection and Characterization of Active Landslides with Multisource SAR Data and Remote Sensing in Western Guizhou, China
Authors: Zhu Yifei , YAO Xin , Yao Leihua , Yao Chuangchuang
Published: July 2021

The western part of Guizhou is located in the second step of East Asia. Although the area is stratigraphically continuous and the surface is dominated by hard limestone and sandstone, catastrophic landslides often occur, seriously threatening residents' lives and the safety of property. Accurate identification of landslides and analysis of their developmental patterns are vital to prevent and reduce the threat of geological disasters. No active landslide survey data cover this region, so this paper identifies the active landslides in the western part of Guizhou by combining surface deformation information, multitemporal optical remote sensing images, geological lithology, and geomorphic features to obtain deformation information from multisource synthetic aperture radar surface data. This process increases the accuracy and reliability of identifying unstable slopes in areas with dense vegetation and steep terrain. By processing 283 Sentinel-1 and PALSAR-2 synthetic aperture radar data, 588 active landslides, 18 of which are high-risk large-scale landslides (landslide groups), are delineated for the first time in a range of 4.64x104 km2 in the study area. The active landslides mainly include resurrected ancient landslides, reservoir/riverbank landslides, and mining-induced landslides, accounting for 2.4%, 4.1%, and 91.8%, respectively. The spatial distribution of landslides is banded along the cuesta at the edge of an outcrop of coal strata. Landslides are mainly distributed at elevations of 1800–2000 m, with an elevation difference of 50 ~ 100 m and a slope range of 35°~40°. The landslides are characterized by steep slopes, small scales, mass occurrences, and no dominant slope direction, classifying them as cuesta landslides induced by mining disturbance. Furthermore, nuanced remote sensing interpretation of the disaster elements, such as cuesta cliff, tensile cracks, deep and sizeable tensile channels, isolated rock masses, and collapse debris, and their processes of change, reveals that coal mining-disturbed landslides in this region have experienced four primary stages: natural unloading, mining disturbance, displacement acceleration, and slope failure. This is of great significance for understanding the genetic mechanism and developmental patterns, as well as the risk assessment, of this region.
Altered RNA splicing initiates the viral mimicry response from inverted SINEs following type I PRMT inhibition in Triple-Negative Breast Cancer
Authors: Arrowsmith Cheryl , Wu Qin , Nie David , alawi Wail , Cruickshank Jennifer , Haight Jillian , Ji YiShuai , Ciamponi Felipe , Shen Yudao , Liu Jing , Chen Jocelyn , Duan Shili , Marhon Sajid , Mehdipour Parinaz , Szewczyk Magdalena , Artun Nergiz , Chen Wenjun , Zhang Lan Xin , Deblois Genevieve , Prinos Panagiotis , Maussirer Katlin , Barsyte-Lovejoy Dalia , Jin Jian , De Carvalho Daniel , Haibe-Kains Benjamin , Cescon David , Lupien Mathieu
Published: July 2021

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here, we undertook a screen of epigenetic chemical probes to systematically uncover the epigenetic regulators critical for TNBC growth. We identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), as having anti-tumor growth activity in TNBC in vitro and in vivo. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses pre- and post-MS023 treatment is a functional biomarker and determinant of response; and these observations extend to a panel of patient-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA (dsRNA). The observed dsRNA accumulation is derived, at least in part, from inverted-repeat Alus (IR-Alus), many of which are expressed from retained introns induced by MS023, which inhibits arginine methylation of RNA-binding proteins and alters mRNA splicing machinery. Together, our results represent a shift in understanding the anti-tumor mechanism of type I PRMT inhibitors and provide a novel rationale and biomarker approach for the clinical development of type I PRMT inhibitors.
A Novel Homozygous Missense Mutation of WEE2 Causes Female Infertility Characterized by Fertilization Failure
Authors: Liu Wenwen , Yan Guijun , Zhang Ningyuan , Kong Na , Wu Min , Fang Junshun , Sun Haixiang
Published: July 2021

Purpose: To investigate the genetic cause of infertility in a female patient due to repeated fertilization failure.Methods: Whole exome sequencing was performed to obtain the candidate mutation. Sanger sequencing was used to identify the mutation of the proband and other family members. SIFT, Polyphen-2, and Mutation Taster were used to predict the pathogenicity of mutations. The online software Arpeggio and the mCSM online service were used to analyze the effect of the mutation on protein structure and stability. Results: We identified a novel homozygous missense mutation c.T1199A:p.L400Q (Leu400Gln) in WEE2 gene in a female proband with infertility caused by fertilization failure. Conclusions: We discovered a novel homozygous missense mutation c.T1199A:p.L400Q (Leu400Gln) of the WEE2 gene in an infertile female whose oocytes had undergone complete fertilization failure, either after ICSI or RICSI. Our findings extend the mutant spectrum of WEE2 , a genetic cause for fertilization failure, and provide a theoretical basis for clinical diagnosis of the pathogenic causes of infertility.
One-axis Two-wing Guest-Host Strategy for Constructing Ultralong-lifetime Near-infrared Organic Phosphorescence Materials for Bioimaging
Authors: Xiao Fuming , Gao Heqi , Lei Yunxiang , Dai Wenbo , Liu Miao-Chang , Zheng Xiaoyan , Cai Zhengxu , Huang Xiaobo , wu Hua-yue , Ding Dan
Published: July 2021

Organic near-infrared room temperature phosphorescence (RTP) materials have unparalleled advantages in bioimaging due to their excellent penetrability. However, limited by the energy gap law, organic matters with long wavelengths (> 700 nm) and long lifetimes (> 100 ms) have not been reported so far. In this work, we have obtained organic RTP materials with long wavelengths (657–732 nm) and long lifetimes (102–324 ms) for the first time through the one-axis two-wing guest-host strategy. The one axis refers to that the guest molecule has sufficient conjugation to reduce the lowest triplet energy level and the two wings refer to that the host assists the guest in exciton transfer and inhibits the non-radiative transition of guest excitons. These materials exhibit good tissue penetration in bioimaging. Thanks to the characteristic of long lifetime and long wavelength emissive RTP materials, the tumor imaging in living mice with a signal to background ratio value as high as 43 is successfully realized. This work provides a practical solution for the construction of organic RTP materials with both long wavelengths and long lifetimes.
The Decoupling of China's Economy-Carbon Emission and Its Driving Factors
Authors: Kuai Peng , Cheng Yao , Zhang Shu'an
Published: July 2021

Decoupling between economic growth and carbon emission is a global hot topic. This paper studies China’s economic-carbon decoupling and its driving factors. By using the panel data of 30 Chinese provinces from 2000 to 2016, the decoupling index of each province is calculated with the Tapio model. It is found that many provinces have progressed from no decoupling to weak decoupling and then strong decoupling. Then, the econometric models are used to explore the driving factors. Results show that energy structure is the most important factor, followed by GDP per capita and energy intensity, which all increase CO2 emission significantly. The results are robust when tested with GMM, PCSE and FGLS estimation and LMDI decomposition. Further, we conduct a comparative analysis regarding the temporal and spatial characteristics of the above three driving factors to identify their relationship with decoupling, four groups of regions that represent different economic features are selected for the analysis. Heterogeneity effects of the factors among the regions has been observed, based on this we provide targeted strategies for different regions.
A Novel Method of Designing an all Optical 3-Bit Asynchronous Counter
Authors: Garai Manas Kumar , Mandal Mrinal Kanti , GARAI SISIR KUMAR
Published: July 2021

In digital signal processing and data communication system in optical domain it is paramount important to count the pulse number of any device or processor and hence optical counter for fast counting. In this letter the authors propose a new method to implement an all-optical 3- bit asynchronous binary counter comprising all-optical T flip flops which works based on the polarization switching characteristics of SOA, and frequency encoded data have been used for communication purpose. Use of Frequency encoding technique in the proposed scheme makes it attractive and effective one in various aspects in wave division multiplexing based communication network. Simulation aided results support the practicability of the proposed scheme.
Using Raw and Thermally Modified Fibrous Clay Minerals as Low Concentration NH4+-N Adsorbents
Authors: Lazaratou Christina Vasiliki , Triantaphyllidou Irene E. , Pantelidis Ioannis , Chalkias Dimitris A. , Kakogiannis George , Vayenas Dimitrios V. , Papoulis Dimitrios
Published: July 2021

Raw and modified fibrous clay minerals palygorskite (Pal) and sepiolite (Sep) were tested for their ability to remove ammonium from ammonium polluted water. Palygorskite and sepiolite underwent thermal treatment at 400oC (T-Pal and T-Sep respectively). Raw and thermally treated samples were characterized using XRD, SEM, BET, FT-IR, TGA, zeta potential and XRF. The techniques verified the effect of thermal treatment on samples structures and the enhancement of negative charge. Both raw and thermally-activated materials applied in batch kinetic experiments, and found to be efficient adsorbents in their raw forms, since Pal and Sep achieved 60 and 80% NH4+-N removal respectively within 20 min of contact for initial NH4+-N concentration of 4 mg/L. Similar removal rates were gained for other concentrations representative of contaminated aquifers that were examined, ranging from 1 mg/L to 8 mg/L. Results for the modified T-Pal and T-Sep minerals showed up to 20% higher removal rate. Saturation tests indicated the positive effect of thermal treatment on the minerals since T-Pal and T-Sep removal efficiency reached 85% and remained stable for 24 h. However, competitive ions in real water samples can influence the NH4+-N removal efficiency of the examined samples. In all cases, the Freundlich isotherm and pseudo-second kinetic models showed better fitted all examined samples thus indicating heterogeneous chemisorption.
Mhealth and Utilization of Health Care Services in Lagos Southwest Nigeria- A Pilot Study
Authors: Osanyin Gbemisola E. , Oluwole Esther O. , Odeseye Adesumbo K. , Afolabi Bosede B.
Published: July 2021

Background: A third of pregnant women in Nigeria do not attend Antenatal care, hence this quasi-experimental study was carried out within 500 consenting pregnant women within the 5 administrative zones of Lagos to determine the association between Mhealth services and utilization of antenatal and skilled delivery services amongst pregnant women in Lagos, Southwest Nigeria.Methods: Participants were divided into an intervention (who received voice messages) and a control arm (did not receive voice messages). Ownership of a mobile phone and willingness to participate were the selection criteria. Data was collected using a structured interviewer administered questionnaire. Analysis was by descriptive statistics with 95% CI to identify factors associated with antenatal attendance.Results: Total respondents were 488 (response rate 97.6%). One hundred and fifty-nine (63.8%) of the intervention group found the messages useful. Using the WHO 2016 ANC model, women in the intervention group had a significantly higher frequency of antenatal care attendance than the control group (p < 0.0001). There was a statistically significant difference in antenatal attendance between the intervention and the controls (p < 0.0001). There was also a significantly lower likelihood of poorly supervised (unskilled) home deliveries within the intervention arm (p=0.011). Conclusion: Mhealth was associated with an increased antenatal attendance and skilled birth attendance at delivery. This has a significant impact in reducing morbidity and mortality indices.
Inflammatory and infectious upper respiratory diseases associate with 59 genomic loci that link to type 2 inflammation genes
Authors: Saarentaus Elmo , Karjalainen Juha , Rämö Joel , Kiiskinen Tuomo , Havulinna Aki , Mehtonen Juha , Hautakangas Heidi , Ruotsalainen Sanni , Salmi Sanna , Pirinen Matti , Kurki Mitja , Ripatti Samuli , Daly Mark , Palotie Tuula , Mäkitie Antti , Palotie Aarno
Published: July 2021

Inflammatory and infectious upper respiratory diseases (IURDs; ICD-10: J30-J39), such as diseases of sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyzed genome-wide association to eight IURDs (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. We aimed to understand which genetic loci contribute to susceptibility to IURDs in general and its subtypes. We detected 59 independent genome-wide significant (GWS) loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in 16 genes, including 10 linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci and inflammatory bowel diseases, and other immune-mediated disorders at pharyngeal disease loci. IURDs also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among IURDs that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.