bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mathematical Model for an Integrated Assembly Line Regarding Learning and Fatigue Effects
Authors: Eslamipoor Reza , Nobari Arash 
Published: January 2021

SUMMARY
In this paper, an integrated mathematical model for the balancing and sequencing problems of a mixed-model assembly line (MMAL) is developed. The proposed model minimizes the total overload and idleness times. For the sake of reality, the impact of operator’s learning and fatigue issues on the optimization of the assembly line balancing and sequencing problems is considered. Furthermore, it is assumed that the Japanese mechanism is used in this assembly line to deal with the overload issue. With respect to the complexity level of the proposed model, a genetic algorithm is developed to solve the model. In order to set the parameters of the developed genetic algorithm, the well-known Taguchi method is used and the efficiency of this solution method is compared with the GAMS software using several test problems with different sizes. Finally, the sensitivity of the balancing and sequencing problems to the parameters such as station length, learning rate, and fatigue rate are analyzed and the impact of changing these parameters on the model is studied.
An evaluation of COVID-19 transmission control in Wenzhou using a modified SEIR model
Authors: Li Wenning , Gong Jianhua , Zhou Jieping , Zhang Lihui , Wang Dongchuan , Li Jing , Shi Chenhui , Fan Hongkui 
Published: January 2021

AbstractIn December 2019, the first confirmed case of pneumonia caused by a novel coronavirus was reported. Coronavirus disease 2019 (COVID-19) is currently spreading around the world. The relationships among the pandemic and its associated travel restrictions, social distancing measures, contact tracing, mask-wearing habits and medical consultation efficiency have not yet been extensively assessed. Based on the epidemic data reported by the Health Commission of Wenzhou, we analysed the developmental characteristics of the epidemic and modified the Susceptible-Exposed-Infectious-Removed (SEIR) model in three discrete ways. (1) According to the implemented preventive measures, the epidemic was divided into three stages: initial, outbreak and controlled. (2) We added many factors, such as health protections, travel restrictions and social distancing, close-contact tracing and the time from symptom onset to hospitalisation (TSOH), to the model. (3) Exposed and infected people were subdivided into isolated and free-moving populations. For the parameter estimation of the model, the average TSOH and daily cured cases, deaths and imported cases can be obtained through individual data from epidemiological investigations. The changes in daily contacts are simulated using the intracity travel intensity (ICTI) from the Baidu Migration Big Data platform. The optimal values of the remaining parameters are calculated by the grid search method. With this model, we calculated the sensitivity of the control measures with regard to the prevention of the spread of the epidemic by simulating the number of infected people in various hypothetical situations. Simultaneously, through a simulation of a second epidemic, the challenges from the rebound of the epidemic were analysed, and prevention and control recommendations were made. The results show that the modified SEIR model can effectively simulate the spread of COVID-19 in Wenzhou. The policy of the lockdown of Wuhan, the launch of the first-level Public Health Emergency Preparedness measures on 23 January 2020 and the implementation of resident travel control measures on 31 January 2020 were crucial to COVID-19 control.
Neighbourhood exceptionalism and racial liberalism in the Great Society city: integration as civic showpiece at St Louis’ LaClede Town
Authors: Looker Benjamin 
Published: January 2021

AbstractThis article analyses the role of LaClede Town, a nationally lauded housing development in St Louis (USA), in metropolitan and national contests over race, segregation and urban equity from the 1960s to 1990s. Built on the site of a massive slum-clearance project, the federally supported complex gained widespread fame for its startlingly heterogeneous racial mix and ostensibly colour-blind lifestyles. As the article argues, the quasi-utopian language applied to the neighbourhood illustrates the contours and limitations of a 1960s racial liberalism that sought to overcome structural inequalities through face-to-face neighbourly contact. Yet the project's 1990s demise signals that older ideology's supersession by a newly dominant urban neoliberalism.
DNA methyltransferase inhibitors modulate histone methylation: epigenetic crosstalk between H3K4me3 and DNA methylation during sperm differentiation
Authors: Burlibaşa Liliana , Nicu Alina-Teodora , Domnariu Carmen 
Published: January 2021

SummaryThe process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate ‘tuning’ of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial–temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.
Understanding productivity effects of hydraulic fracturing in unconventional natural gas deposits and implications for adoption in the developing world
Authors: Fitzgerald Timothy , Mason Charles F. 
Published: January 2021

AbstractHydraulic fracturing (HF) has transformed the North American oil and gas industry, leading to increased consumer surplus and reduced carbon emissions. While HF may have similar potential for the developing world, adoption has been limited to date, plausibly because of perceptions of potential local costs and the need to develop technical proficiency. We empirically evaluate the incremental contribution of HF in the United States. We find considerable evidence of differences in application and productivity across operating firms and vertical pairings of firms, suggesting intellectual property and learning by doing may both play important roles. At the same time, secrecy regarding the chemical composition of fluids used in HF is a potential deterrent to its application for fear of local costs. Developing countries must accommodate these characteristics if adoption of HF is to help meet energy demands and achieve climate policy goals.
Genetic resources of Asian palmyrah palm (Borassus flabelliferL.): a comprehensive review on diversity, characterization and utilization
Authors: Siju S. , Sabu K. K. 
Published: January 2021

AbstractAsian palmyrah palm (Borassus flabelliferL.) is a multipurpose, economically important tree widely distributed in the Indian subcontinent and Southeast Asia. The multifaceted uses (~800 uses) of the tree as food, wood and medicine make it a viable industrial crop. However, the dioecious nature of the tree coupled with long juvenile phase (12–20 years to initiate flowering), long stature and considerable variations in the productivity of male and female trees necessitates the application of new biotechnological tools for crop improvement. This review provides comprehensive information on the extent of genetic diversity of the crop, problems associated with palmyrah cultivation along with its multifaceted application and research gaps to be addressed for the effective utilization and conservation of palmyrah palm genetic resources.
Angle and polarization-independent miniaturized UWB FSS design
Authors: Yuan Yanning , Zhao Yuchen , Xi Xiaoli 
Published: January 2021

AbstractA single-layer ultra-wideband (UWB) stop-band frequency selective surface (FSS) has several advantages in wireless systems, including a simple design, low debugging complexity, and an appropriate thickness. This study proposes a miniaturized UWB stop-band FSS design. The proposed FSS structure consists of a square-loop and metalized vias that are arranged on a single layer substrate; it has an excellent angle and polarization-independent characteristics. At an incident angle of 60°, the polarization response frequencies of the transverse electric and magnetic modes only shifted by 0.003 f0 and 0.007 f0, respectively. The equivalent circuit models of the square-loop and metallized vias structure are analysed and the accuracy of the calculation is evaluated by comparing the electromagnetic simulation. The 20 × 20 array constitutes an FSS reflector with a unit size of 4.2 mm × 4.2 mm (less than one-twentieth of the wavelength of 3 GHz), which realizes an UWB quasi-constant gain enhancement (in-band flatness is <0.5 dB). Finally, the simulation results were verified through sample processing and measurement; consistent results were obtained. The FSS miniaturization design method proposed in this study could be applied to the design of passband FSS (complementary structure), antennas and filters, among other applications.
METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner
Authors: Pan Xiaoping , Hong Xiaolv , Li Sumei , Meng Ping , Xiao Feng 
Published: January 2021

AbstractBreast cancer (BC) is the most prevalent malignant neoplasm among women and is the fifth most common cause of cancer-associated death worldwide. Acquired chemoresistance driven by genetic and epigenetic alterations is a significant clinical challenge in treating BC. However, the mechanism of BC cell resistance to adriamycin (ADR) remains to be elucidated. In this study, we identified the methyltransferase-like 3/microRNA-221-3p/homeodomain-interacting protein kinase 2/Che-1 (METTL3/miR-221-3p/HIPK2/Che-1) axis as a novel signaling event that may be responsible for resistance of BC cells to ADR. A dual-luciferase reporter gene assay was employed to test the presence of miR-221-3p binding sites in the 3′UTR of HIPK2. Drug resistance was evaluated by immunoblotting multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP). Cultured ADR-resistant MCF-7 cells were assayed for their half maximal inhibitory concentration (IC50) values and apoptosis using an MTT assay and Annexin V-FITC/PI-labeled flow cytometry, and the cells were then xenografted into nude mice. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, thereby reducing the IC50 value of ADR-resistant MCF-7 cells, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Mechanistically, miR-221-3p was demonstrated to negatively regulate HIPK2 and upregulate its direct target Che-1, thus leading to enhanced drug resistance in ADR-resistant MCF-7 cells. In vitro results were reproduced in nude mice xenografted with ADR-resistant MCF-7 cells. Our work elucidates an epigenetic mechanism of acquired chemoresistance in BC, in support of the METTL3/miR-221-3p/HIPK2/Che-1 axis as a therapeutic target for the improvement of chemotherapy.
Role of connexin 43 in odontoblastic differentiation and structural maintenance in pulp damage repair
Authors: Yin Jiaxin , Xu Jue , Cheng Ran , Shao Meiying , Qin Yuandong , Yang Hui , Hu Tao 
Published: January 2021

AbstractDental pulp can initiate its damage repair after an injury of the pulp–dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp–dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.
Novel MSX1 variants identified in families with nonsyndromic oligodontia
Authors: Zheng Jinglei , Yu Miao , Liu Haochen , Cai Tao , Feng Hailan , Liu Yang , Han Dong 
Published: January 2021

AbstractThe goal of this study was to identifyMSX1gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novelMSX1heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed theMSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.
TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia
Authors: Ochiiwa Hiroaki , Ailiken Guzhanuer , Yokoyama Masataka , Yamagata Kazuyuki , Nagano Hidekazu , Yoshimura Chihoko , Muraoka Hiromi , Ishida Keiji , Haruma Tomonori , Nakayama Akitoshi , Hashimoto Naoko , Murata Kazutaka , Nishimura Motoi , Kawashima Yusuke , Ohara Osamu , Ohkubo Shuichi , Tanaka Tomoaki 
Published: January 2021

AbstractTAS4464, a potent, selective small molecule NEDD8-activating enzyme (NAE) inhibitor, leads to inactivation of cullin-RING E3 ubiquitin ligases (CRLs) and consequent accumulations of its substrate proteins. Here, we investigated the antitumor properties and action mechanism of TAS4464 in acute myeloid leukemia (AML). TAS4464 induced apoptotic cell death in various AML cell lines. TAS4464 treatments resulted in the activation of both the caspase-9-mediated intrinsic apoptotic pathway and caspase-8-mediated extrinsic apoptotic pathway in AML cells; combined treatment with inhibitors of these caspases markedly diminished TAS4464-induced apoptosis. In each apoptotic pathway, TAS4464 induced the mRNA transcription of the intrinsic proapoptotic factor NOXA and decreased that of the extrinsic antiapoptotic factor c-FLIP. RNA-sequencing analysis showed that the signaling pathway of the CRL substrate c-Myc was enriched after TAS4464 treatment. Chromatin immunoprecipitation (ChIP) assay revealed that TAS4464-induced c-Myc bound to the PMAIP1 (encoding NOXA) and CFLAR (encoding c-FLIP) promoter regions, and siRNA-mediated c-Myc knockdown neutralized both TAS4464-mediated NOXA induction and c-FLIP downregulation. TAS4464 activated both caspase-8 and caspase-9 along with an increase in NOXA and a decrease in c-FLIP, resulting in complete tumor remission in a human AML xenograft model. These findings suggest that NAE inhibition leads to anti-AML activity via a novel c-Myc-dependent apoptosis induction mechanism.
Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma
Authors: Xu Yinyin , Guo Jing , Liu Jing , Xie Ying , Li Xin , Jiang Hongmei , Wang Jingjing , Peng Ziyi , Wang Jingya , Wang Sheng , Wan Chao , Chen Lanting , Zhong Yuping , Liu Beizhong , Liu Zhiqiang 
Published: January 2021

AbstractMyeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotesDKK1expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activateDKK1transcription. In addition, high levels of DKK1 were associated with the presence of focal bone lesions in patients with t(4;14) MM, overexpressing the histone methyltransferase MMSET, which was identified as a downstream target gene of hypoxia-inducible factor (HIF)-1α. Furthermore, we found that CREB could recruit MMSET, leading to the stabilization of HIF-1α protein and the increased dimethylation of histone H3 at lysine 36 on the DKK1 promoter. Knockdown of CREB in myeloma cells alleviated the suppression of osteoblastogenesis by myeloma-secreted DKK1 in vitro. Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.
Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance
Authors: Yoshida Kosuke , Yokoi Akira , Sugiyama Mai , Oda Shingo , Kitami Kazuhisa , Tamauchi Satoshi , Ikeda Yoshiki , Yoshikawa Nobuhisa , Nishino Kimihiro , Niimi Kaoru , Suzuki Shiro , Kikkawa Fumitaka , Yokoi Tsuyoshi , Kajiyama Hiroaki 
Published: January 2021

AbstractOvarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer and exhibits dismal prognosis due to chemoresistance. Moreover, only few effective therapeutic options exist for patients with recurrent OCCC, and an understanding of its molecular characteristics is essential for the development of novel therapeutic approaches. In the present study, we investigated unique MicroRNAs (miRNA) profiles in recurrent/metastatic OCCC and the role of miRNAs in cisplatin resistance. Comprehensive miRNA sequencing revealed that expression of several miRNAs, including miR-508-3p, miR-509-3p, miR-509-3-5p, and miR-514a-3p was remarkably less in recurrent cancer tissues when compared with that in paired primary cancer tissues. These miRNAs are located in the chrXq27.3 region on the genome. Moreover, its expression was negative in omental metastases in two patients with advanced OCCC. In vitro analyses revealed that overexpression of miR-509-3p and miR-509-3-5p reversed cisplatin resistance and yes-associated protein 1 (YAP1) was partially responsible for the resistance. Immunohistochemistry revealed that YAP1 expression was inversely correlated with the chrXq27.3 miRNA cluster expression. In conclusion, these findings suggest that alteration of the chrXq27.3 miRNA cluster could play a critical role in chemoresistance and miRNAs in the cluster and their target genes can be potential therapeutic targets.
β-Trcp and CK1δ-mediated degradation of LZTS2 activates PI3K/AKT signaling to drive tumorigenesis and metastasis in hepatocellular carcinoma
Authors: Lu Yanwei , Li Xudong , Liu Hongli , Xue Jun , Zeng Zhen , Dong Xiaorong , Zhang Tao , Wu Gang , Yang Kunyu , Xu Shuangbing 
Published: January 2021

AbstractDistant metastasis is the leading cause of treatment failure in patients with hepatocellular carcinoma (HCC). However, the underlying mechanisms have not been fully elucidated. Here, we report that Leucine zipper tumor suppressor 2 (LZTS2) is downregulated and correlated with poor prognosis in HCC. Furthermore, we provide evidence that LZTS2 associates with p85 to inhibit the activation of PI3K/AKT signaling and impairs HCC tumorigenesis and metastasis in vitro and in vivo. Moreover, we identify LZTS2 as a bona fide substrate of the E3 ligase β-Trcp and protein kinase CK1δ, which are responsible for the ubiquitination and degradation of LZTS2. Importantly, we show that the β-Trcp and CK1δ-mediated degradation of LZTS2 promotes HCC progression and metastasis by activating PI3K/AKT signaling. Collectively, our study not only illustrates the roles of LZTS2 in regulating HCC tumorigenesis and metastasis but also reveals a novel posttranslational modification of LZTS2 by β-Trcp and CK1δ, indicating that the β-Trcp/CK1δ/LZTS2/PI3K axis may be a novel oncogenic driver involved in HCC progression and metastasis.
Loss and revival of androgen receptor signaling in advanced prostate cancer
Authors: Formaggio Nicolò , Rubin Mark A. , Theurillat Jean-Philippe 
Published: January 2021

AbstractTargeting the androgen receptor (AR) signaling axis has been, over decades, the mainstay of prostate cancer therapy. More potent inhibitors of androgen synthesis and antiandrogens have emerged and have been successfully implemented in clinical practice. That said, the stronger inhibition of the AR signaling axis has led in recent years to an increase of prostate cancers that de-differentiate into AR-negative disease. Unfortunately, this process is intimately linked with a poor prognosis. Here, we review the molecular mechanisms that enable cancer cells to switch from an AR-positive to an AR-negative disease and efforts to prevent/revert this process and thereby maintain/restore AR-dependence.