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There are many emergency risks in the process of natural gas hydrate (NGH) drilling. In order to ensure the safe and efficient exploitation of NGH, it is urgent to establish an intelligent judgment method for the risks in the process of NGH drilling. In this paper, the response relationship between monitoring parameters and risk categories of NGH while drilling is established. Based on fuzzy analytic hierarchy process (FAHP), the comprehensive weights of 10 risk monitoring parameters are obtained, including gas production, wellbore instability, hydrate ice barrier, drill string fracture, sticking, bit balling, drilling tool piercement, gas seepage, seabed subsidence and seabed landslide. Besides, the comprehensive judgment weight matrix is constructed, and the reasonable fluctuation range of monitoring parameters is formed. Thus, the intelligent judgment method of NGH drilling risk is established. The intelligent judgment and alarm of NGH drilling risks can be realized quickly and accurately by this method, namely, it can monitor the risks in the process of operation and guarantee the construction safety of NGH drilling.

PurposeThe objective of this study was to improve understanding of frontline staff's subjective happiness and anxiety during the COVID-19 pandemic by investigating the roles of employees' busy mindset and leader conscientiousness.Design/methodology/approachThe link between employee anxiety and subjective happiness was also explored, and the cross-level mediating effect of employee anxiety was tested using a multilevel design. A survey of 373 frontline staffers and 74 team leaders in the integrated resorts (IRs) was conducted in three waves: April (Time 1), May (Time 2) and June (Time 3) in 2020. The data were analysed with SPSS and Mplus using a hierarchical linear modelling (HLM) method.FindingsThe results indicated that during the COVID-19 pandemic, a busy mindset increased frontline staff's anxiety and thus decreased their subjective happiness, and leader conscientiousness remedied the effect of anxiety on subjective happiness.Practical implicationsThe findings are relevant to frontline staffers, team leaders in the hospitality industry and corporate service departments. Against the background of COVID-19, conscientious leaders can significantly help employees to overcome their anxiety and insecurity and improve their subjective happiness, answering the urgent call to deal with the challenges of the new work–life environment.Originality/valueThe study differs from previous other studies in two dimensions: First, the authors explored the interactions of the affective events from the cross-level perspectives, i.e. both team level and individual level. Second, the authors conducted this research on the mental issues of the hospitality frontline staffers in the context of the COVID-19 pandemic, which remains a black box to be explored.

Chromatin-modifying enzymes, especially protein arginine methyltransferases (PRMTs), have been identified as candidate targets for cancer. Cellular or animal-based evidence has suggested an association between coactivator-linked arginine methyltransferase 1 (CARM1) and cancer progression. However, the relationship between CARM1 and patient prognosis and immune infiltration in pancancer patients is unknown. On the basis of the GEO and TCGA databases, we first investigated the possible oncogenic functions of CARM1 in thirty-three tumor types. CARM1 expression was elevated in many types of tumors. In addition, there was a significant association between CARM1 expression and the survival rate of tumor patients. Uterine corpus endometrial carcinoma (UCES) samples had the highest CARM1 mutation frequency of all cancer types. In head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), CARM1 expression was associated with the level of CD8+ T cell infiltration, and cancer-associated fibroblast infiltration was also observed in other tumors including kidney renal papillary cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). CARM1 was involved in immune modulation and played an important role in the tumor microenvironment (TME). Furthermore, activities associated with RNA transport and its metabolism were included in the possible mechanisms of CARM1. Herein, our first pancancer research explores the oncogenic role of CARM1 in various tumors. CARM1 is associated with immune infiltrates and can be employed as a predictive biomarker in pancancer.

PurposeGiven the heightened imperatives for boosting supply chain resilience (SCR) in industrialized construction (IC), it is essential to explore the correlational impacts of supply chain vulnerabilities (SCV) and supply chain capabilities (SCC) which are the measures of SCR, specifically in Hong Kong where policymakers actively promote IC. Therefore, this study aims to develop a model to explore the correlational impacts of vulnerabilities and capabilities targeting SCR in IC.Design/methodology/approachAfter drawing on the general literature on SCR, empirical research using an expert opinion survey was conducted following the methodological framework of this study. The gathered data were then subjected to the partial least squares structural equation modeling process. Thereby, four hypotheses were formulated and tested for 20 capability–vulnerability relationships.FindingsSeven of the 20 statistical relationships tested were identified to be significant. Accordingly, production-based SCV were identified as the most critical disruptions. “Resourcefulness” could substantially withstand production-based SCV, receiving the highest path significance. An “enablers-results framework” for achieving SCR of IC was also developed based on these findings to help industry practitioners with SCR implementation.Originality/valueTo the authors' knowledge, this is the first structured evaluation model that measures the correlational impacts of SCC and SCV targeting SCR in the construction domain. Further, this study adds substantially to the existing SCR and construction “body of knowledge” by proposing a model explaining how various SCV and SCC influence SCR in IC. These findings also inform the industry where and how to deploy critical SCC at appropriate levels, targeting critical SCV, to contain or extirpate them.

Silicon photonics realized in CMOS processes has transformed computing, communications, sensing, and imaging. Although silicon is an indirect bandgap material prohibiting efficient light generation, considerable work has been conducted in the field of silicon p-n junctions emitting broadband visible light when operating in the high-voltage reverse breakdown avalanching mode. Here, we demonstrate high-brightness near-infrared (NIR) light emission for forward-biased silicon micro-light emitting diodes (micro-LEDs) realized in an open-foundry microelectronic CMOS process—55 BCDLite—with zero modification. Under room-temperature continuous-wave operation, the external light emission intensity of over 40 mW/cm $^{{2}}$ at a central wavelength of 1020 nm is achieved for a 4- $\mu \text {m}$ -diameter device at below 2.5 V. This is realized by adopting a deep vertical junction with guard ring designs that ensure carrier transport away from the device surface and material interfaces where nonradiative recombination usually dominates. Here, we also demonstrate a complete chip-to-chip communication link using only standard multimode fiber and monolithically integrated CMOS micro-LEDs and detectors.

PurposeThis study aims to examine how the clickbait headlines influence the perceived source credibility, subjective norm, perceived benefit and purchasing intention of customers on social commerce through social media platforms in different interpersonal relationship strength scenarios.Design/methodology/approachA total of three studies were employed online to test the hypotheses. Study 1 used a single-factor, two-condition (clickbait: yes vs no) between-subject design. Both study 2 and study 3 employed a 2 (clickbait: yes vs no) × 2 (relationships: close friend vs stranger) between-subject design. All data were sourced randomly from 729 respondents in China. Data and models were analyzed by using SPSS and Mplus.FindingsStudy 1 illustrated that clickbait has a negative effect on perceived credibility and purchase intention, and the perceived credibility mediated the relationship between clickbait and purchase intention. Study 2 replicated such finding and demonstrated that the interpersonal relationship strength interacts with the influence from clickbait to purchase intention. Study 3 enhanced the mechanism of source credibility found in the above studies and further revealed that perceived benefit and perceived norm had a mediating role in the purchase-making process online.Originality/valueResearch efforts to date concentrate on how to detect and reduce clickbait headlines. This paper adopts a different perspective, considering the consequences of clickbait in the marketing domain. This study reveals the effects of clickbait on purchase intention and the mechanism behind this process under different scenarios.

The task of automated essay scoring (AES) continues to attract interdisciplinary attention due to its commercial and educational importance as well as related research challenges. Traditional AES approaches rely on handcrafted features, which are time-consuming and labor-intensive. Neural network approaches have recently given fantastic results in AES without feature engineering, but they usually require extensive annotated data. Moreover, most of the existing AES models only report a single holistic score without providing diagnostic information about various dimensions of writing quality. Focusing on these issues, we develop a novel approach using multi-task learning (MTL) with fine-tuning Bidirectional Encoder Representations from Transformers (BERT) for multi-dimensional AES tasks. As a state-of-the-art pre-trained language model, a BERT-based approach can improve AES tasks with limited training data. Meanwhile, we deal with long texts by proposing a hierarchical method and using the attention mechanism to automatically determine the contribution of different fractions of the input essay to the final score. For the multi-topic essay scoring tasks on the ASAP dataset, results reveal that our approach outperforms the average quadratic weighted Kappa (QWK) score by 4.5% compared with the strong baseline. We propose a self-collected dataset of Chinese EFL Learners’ Argumentation (CELA) to provide valuable information about writing quality from multiple rating dimensions, including holistic and five analytic scales. For the multi-rating dimensional essay scoring tasks on the CELA dataset, experimental results demonstrate that our model increases the average QWK score by 8.1% compared with the strong baseline.

Pulmonary route of drug delivery has drawn significant attention due to the limitations associated with conventional routes and available treatment options. Drugs administered through pulmonary route has been an important research area that focuses on to developing effective therapeutic interventions for asthma, chronic obstructive pulmonary disease, tuberculosis, lung cancer etc. The intravenous route has been a natural route of delivery of proteins and peptides but associated with several issues including high cost, needle-phobia, pain, sterility issues etc. These issues might be addressed by the pulmonary administration of macromolecules to achieving an effective delivery and efficacious therapeutic impact. Efforts have been made to develop novel drug delivery systems (NDDS) such as nanoparticles, microparticles, liposomes and their engineered versions, polymerosomes, micelles etc to achieving targeted and sustained delivery of drug(s) through pulmonary route. Further, novel approaches such as polymer-drug conjugates, mucoadhesive particles and mucus penetrating particles have attracted significant attention due to their unique features for an effective delivery of drugs. Also, use of semi flourinated alkanes is in use for improvising the pulmonary delivery of lipophilic drugs. Present review focuses on to unravel the mechanism of pulmonary absorption of drugs for major pulmonary diseases. It summarizes the development of interventional approaches using various particulate and vesicular drug delivery systems. In essence, the orchestrated attempt presents an inflammatory narrative on the advancements in the field of pulmonary drug delivery.

ObjectiveTo determine whether the GGC repeats in the NOTCH2NLC gene contribute to amyotrophic lateral sclerosis (ALS).MethodsIn this study, 545 patients with ALS and 1,305 healthy controls from mainland China were recruited. Several pathogenic mutations in known ALS-causative genes (including C9ORF72 and ATXN2) and polynucleotide repeat expansions in NOP56 and AR genes were excluded. Repeat-primed PCR and GC-rich PCR were performed to determine the GGC repeat size in NOTCH2NLC. Systematic and targeted clinical evaluations and investigations, including skin biopsy and dynamic electrophysiologic studies, were conducted in the genetically affected patients.ResultsGGC repeat expansion was observed in 4 patients (numbers of repeats 44, 54, 96, and 143), accounting for ≈0.73% (4 of 545) of all patients with ALS. A comparison with 1,305 healthy controls revealed that GGC repeat expansion in NOTCH2NLC was associated with ALS (Fisher exact test, 4 of 545 vs 0 of 1,305, p = 0.007). Compared to patients with the neuronal intranuclear inclusion disease (NIID) muscle weakness–dominant subtype, patients with ALS phenotype carrying the abnormal repeat expansion tended to have a severe phenotype and rapid deterioration.ConclusionOur results suggest that ALS is a specific phenotype of NIID or that GGC expansion in NOTCH2NLC is a factor that modifies ALS. These findings may help clarify the pathogenic mechanism of ALS and may expand the known clinical spectrum of NIID.

Construction projects require the effective collaboration among the various types of stakeholders involved to succeed, thus leading to stakeholder perspective studies in construction projects. The study proposes an integrated bibliometric approach to detect the knowledge evolution, domain and frontier with a broader searching scope compared with manual review. A total of 752 peer-reviewed academic papers published until the end of 2017 are used. The knowledge evolution indicates seven milestones in history, namely, stakeholder concept, method, identification, assessment, management, influence and complexity. The identified knowledge domain consists of four major research areas which are society, sustainability, analytical tool and project management. The knowledge frontier is also revealed, including a dearth of detailed discussions on stakeholder engagement in sustainable urban projects, lack of generalisation of stakeholder studies in complex construction projects, limited application of dynamic and simulation stakeholder analysis in uncertain project environment and few instant and accurate approaches to integrate stakeholder information. The study provides a holistic knowledge map for the past, current and future of stakeholder perspective studies in construction projects.

PurposeThe purpose of this research is to seek better relational strategies between formal and informal stakeholder relationships to improve megaproject performance.Design/methodology/approachThe conceptual model was developed with twenty hypotheses based on the literature review. Then a questionnaire survey was conducted, and the collected data were analyzed by Partial Least squares Structural Equation Modeling (PLS-SEM) for validating the proposed model. Finally, the findings were discussed by a comparative study to explain the different effects of the formal and informal relationship on megaproject performance, and the managerial implications are presented for the stakeholders to implement the relationship management in the megaprojects.FindingsThe research finding reveals that formal relationship plays a dominating role in cost, quality, and labor protection; meanwhile, it is still more reliable in improving coordination, safety and environmental protection. Both formal and informal relationship is equally important towards collaboration and scheduling while the informal relationship is more effective in communication and project transparency.Originality/valueThe study extends the knowledge of relationship management in the domain of the megaproject performance. It provides a comprehensive and systematic understanding of the impact of formal and informal stakeholder relationships on ten aspects of the megaproject performance by the proposed conceptual model and PLS-SEM results. The research findings contribute to the theory of relationship management on how the different influences between formal and informal stakeholder relationships lead to better megaproject performance from inter-organizational level to project and societal level.

Dockless bike-sharing has provided a flexible and convenient travel mode in recent years, with which shared bikes can be rented and returned easily. However, addressing the imbalance between demand and supply effectively becomes a major challenge to guarantee the sustainability of such systems. Vehicle-based approach results in substantial operating costs and more emissions. This study proposed a user-based model to incentivize users to participate in bike rebalancing. This model contains three important components: 1) determination of a bike surplus region by sorting surplus level in descend order; 2) determination of a bike deficient region from the perspective of users' utility maximization; and 3) updating the states of regions. Several numerical tests were implemented to evaluate the model's performance based on predefined parameters and historical trip data in downtown of Nanjing. As the results indicate, unmet demand can be greatly reduced if providing a certain level of monetary incentive. Different values of the maximum acceptable walking distance make little difference in demand loss and operating cost at a low level of incentive. With regard to the users, it implies that higher proportion of cooperative customers who are willing to participate in rebalancing can lead to a larger reduction of unmet demand. In addition, using surplus level as the index to define bike surplus regions is beneficial to saving the overall operating cost.

Carbon emission quantifications in China are not consistent, with many standards and methods having been used over the years. This study identified the non-consideration of China-specific technology and databases as a factor limiting comprehensive quantification. The study aimed to comprehensively quantify regional direct CO2 emission in the industry using a hybrid of economic and environmental data. We retrieved nineteen (19) sets of fossil fuel and electricity data from provincial energy yearbooks between 1997 and 2015 for the study. To generate regression models for each of the six regional construction industries in China, the study further integrated the results with three sets of econometric data: total annual construction output, cement, and steel product yearly consumption data. The study identified the North China region as the main source of direct CO2 emission with over 30%, while Southeast China contributed the least. While there is a gradual shift to other energy sources, the study identified coal and crude oil to remain as the main energy sources in the industry. Cement and steel data exhibited a significant predictive relationship with CO2 emissions in five regional construction industries. The study identified the need to have policies tailored to technological improvements to enhance renewable energy generation and usage in the industry. The models developed in this study could be used to generate initial quantifications of carbon emissions in construction industries with similar carbon-emitting characteristics for carbon tracking, and energy policies for decision making. However, the three economic indicators used in the study could be extended to generate more robust models in future research.

Background: Hepatocellular carcinoma (HCC), which is the most common type of primary liver cancer, often presents at advanced stage with a dismal prognosis. Novel tumor biomarkers are needed to aid in HCC early detection and prognostication. Methods: Immunohistochemical staining for RecQ-mediated genome instability protein 2 (RMI2) was performed in 330 surgically resected HCC specimens and 190 adjacent normal tissues. Univariate and multivariate regression analysis were applied to identify prognostic indicators of HCC outcomes. Patient's survival was assessed with the Kaplan–Meier method. Results: RMI2 in HCC tissue was significantly higher than that in adjacent normal tissues, and was positively correlated with HCC histological grade and stage ( P

This study sought to evaluate and summarize the best evidence on postural change in the prevention of pressure injuries among critically ill adult patients, to provide a reference for the treatment of these patients in clinical practice.An evidence-based approach was adopted to retrieve relevant articles from databases and professional websites. The Joanna Briggs Institute evidence appraisal and recommendation system was used to assess the quality and level of the evidence.In total, 11 articles were included in the analysis, including 4 clinical practice guidelines, 2 expert consensus papers, 1 evidence summary, 3 systematic reviews, and 1 randomized controlled trial. 14 pieces of evidence on the feasibility and suitability of specific clinical situations were summarized, and the following 7 aspects were considered: (I) individual assessment; (II) postural change frequency; (III) postural change angle; (IV) postural change strategies for critically ill patients with hemodynamic instability; (V) assessment during postural change, (VI) multidisciplinary team cooperation; and (VII) education and training.Clinical nurses should pay attention to the prevention and management of pressure injuries in critically ill adult patients. The approach should be selected and applied according to the specific clinical situation and the individual situation of each patient to achieve better treatment effect.

Prefabricated construction as a preferred construction approach instigated significant technological advancements in construction supply chains in Hong Kong (HK). The Hong Kong-Zhuhai-Macao Bridge (HZMB) was a milestone prefabricated construction project which was successfully constructed using these industrial advancements. However, the project itself was a great challenge as it was highly vulnerable to disruptions due to complex supply chain processes. In this regard, increased resilience could be the key to boosting project performance through enhanced Supply Chain Capabilities (SCCs), where identifying SCC dynamics becomes essential. Therefore, this study employed the Topic Over Time Modeling approach to detect critical SCCs using 1,748 unstructured official documents on the HZMB from 2003 to 2018, which spans the period from project design to handover. The popularity trend analysis of texts enabled identifying the six most critical capabilities associated with each construction phase of planning, construction and handover. Thereafter, an ex-post capability evaluation map was developed by considering the popularity trend of capabilities and their relevance to different project phases. Industry practitioners would benefit from prior knowledge of SCCs and their dynamic impact on each project phase to prioritize initiating them adequately and appropriately, targeting value-enhanced-resilient supply chains in ex-ante decision-making of future prefabricated infrastructure development projects. Further, the text-mining research approach unveils to academia, an effective and novel mechanism to extract dynamic empirical clues from a large unstructured set of documents in construction SCC analysis research.

Public concerns exert far-reaching influence on various phases of megaprojects, requiring the decision makers to achieve dynamic analysis in the aspects of identification, measurement, and ...

The selection of highway alignment without explicit consideration of the interests and preferences of stakeholders is a major recipe for conflicts and opposition in highway projects. Given the complex and dynamic nature of the highway alignment decision atmosphere, a dynamic framework is imperative. This research evaluated three multi-criteria decision methods (MCDMs), identified the optimal combination and proposed a highway alignment decision support framework which embraces the preferences of stakeholders. The proposed framework was validated using a controversial ongoing mega highway project from the China Pakistan Economic Corridor (CPEC). Thus, the study makes a useful contribution to the praxis and practice of the highway alignment decision-making process.

Endogenous cardiac regeneration has been focused for decades as a potential therapy for heart diseases with cell loss, and dimethyl sulfoxide (DMSO) has been proposed as a treatment for many diseases. In this study, we aimed to investigate the function of DMSO on fetal cardiomyocyte proliferation. By tracing BrdU+/α actinin+ cells or Ki67+/α actinin+ cells with immunohistochemical staining, we found that DMSO remarkably promoted fetal cardiomyocytes proliferation, and at the late developmental stage (LDS), such effects were more efficient than that at early developmental stage (EDS). Western blot data revealed a significant increase in STAT3 phosphorylation under DMSO treatments at LDS, while not at EDS. Consistently, STAT3 phosphorylation blocker STA21 could greatly reverse DMSO's function at LDS whereas hardly at EDS. Moreover, hearts at the EDS had less total STAT3 protein, but relatively much higher level of phosphorylated STAT3. This suggests that DMSO promote fetal cardiomyocytes proliferation, and STAT3 phosphorylation play a pivotal role in DMSO's function. With maturation, DMSO exerted a better ability to favor cardiomyocyte proliferation depending on STAT3 phosphorylation. Therefore, DMSO could serve as an effective, economic, and safe therapy for heart diseases with cell loss.

Aims SOX11 is known as an essential transcription factor for regulating neurogenesis. Recently, SOX11 has been suggested to be a diagnostic marker and oncogene because of its significant expression in mantle cell lymphoma (MCL). However, SOX11 expression in other tumour types has not yet been extensively studied. Methods and results Herein, we examined SOX11 expression in 2026 cases of neuroectodermal, germ cell, mesenchymal and epithelial tumours by immunohistochemistry. SOX11 was consistently expressed in all neuroectodermal tumours with neural differentiation, as well as in immature teratomas revealing neurogenesis. Less frequently, SOX11 expression was observed in only 50% of astrocytomas and 24% of malignant peripheral nerve sheath tumours, and was mainly sporadic and weak/intermediate. In epithelial tumours, significant SOX11 expression was identified in 97% of salivary ductal carcinomas (SDCs) and a high percentage of high-grade neuroendocrine carcinomas (NECs), especially the small-cell lung carcinomas (68%), and was absent in most other carcinomas, except for less and/or focal and weak expression in adenocarcinomas from the lung, genital tract and breast, and salivary adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. In mesenchymal tumours, in addition to MCLs, prominent SOX11 expression was observed in 90% of rhabdomyosarcomas and all myxoid/round cell liposarcomas (MRCLs). Less frequent and/or focal and weak expression was observed in lymphoblastic, Burkitt and follicular lymphomas, synovial sarcoma and angiosarcoma. Conclusion SOX11 showed prominent expression in neuroectodermal tumours with neural differentiation, high grade-NEC, SDC, rhabdomyosarcoma and MRCL. The high sensitivity and specificity of SOX11 in SDC and MRCL make it a useful diagnostic marker.

BACKGROUND This study aimed to evaluate the C-reactive protein to serum albumin ratio (CAR) to predict prognosis in COPD patients with acute exacerbations (AECOPD). METHODS A retrospective cohort study of AECOPD patients, admitted to a large tertiary hospital between January 2017 and June 2018, was conducted. Univariate and multivariate logistic regression models were built to assess the relationship between variables and different clinical outcomes in one-year follow up. In addition, Kaplan-Meier method was used to estimate the relationship between CAR and the time to first rehospitalization due to acute exacerbation of COPD. RESULTS A total of 167 AECOPD patients were included in this study, with an overall age of 68.5 ± 9.4 years. Both univariate and multivariate logistic regression analysis demonstrated that CAR at admission was significantly associated with rehospitalization and frequent exacerbations in COPD patients (p < 0.05). Kaplan-Meier curve showed that the rehospitalization event-free rate was significantly higher in the low CAR group than the high CAR group (p < 0.01). CONCLUSIONS As an easily available parameter, CAR at admission can be an independent predictor for rehospitalization and frequent exacerbations in COPD patients with acute exacerbations.

Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice (ApoE−/−), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, p < 0.05 vs. Air 8.1 ± 0.8%, p < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, p < 0.05). The most differentially abundant microbial families (p < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites (p < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.

Financial capital plays a very important role in the cultural industry which has high sunk costs and volatile returns. Therefore, studying the impacts of cultural finance policy on the financing efficiency of cultural corporates has practical significance. This paper used a sample of listed non-financial firms from 2006 to 2018 and studied the association between cultural finance policy and the financing efficiency of cultural corporates based on the information asymmetry theory and principal-agent theory. The empirical research results show that cultural finance policy significantly increases cultural corporates’ financing efficiency. These results enlarged the research content of cultural corporate and provide theoretical guidance for supporting the development of cultural corporate.

Public concerns are essential for megainfrastructure project success, meanwhile profoundly influencing stakeholder performance. To understand the dynamics of public concerns and the project...

Stakeholder conflicts are hard to avoid in the implementation of megaprojects due to the diverse interests and aims among stakeholders. The previous study does not provide much evidence on ...

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe cerebrovascular accident with high morbidity and mortality. The aim of this study is to investigate the relationship between level of inflammatory cytokines in cerebrospinal fluid (CSF) of aSAH patients, the severity of aSAH, and the outcome of aSAH patients.aSAH patients were prospectively included and followed-up for 6 months. CSF samples were collected at 1-3, 4-6, and 7-9 days after aSAH onset. Levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α) in the CSF of aSAH patients were measured by enzyme-linked immunosorbent assay.Eighty-one aSAH patients were enrolled. The levels of IL-1β, IL-18 and TNF-α in the CSF were especially higher in the group of aSAH patients with cerebral edema, cerebral vasospasm, and a high grade on Hunt-Hess scale, the high World Federation of Neurological Surgeons grades, and Fisher grade (P0.01). Higher levels of plasma C-reactive protein in the blood were correlated with poor outcome. The areas under the receiver operating characteristic curves for the levels of inflammatory cytokines in CSF were 0.85, 0.84, and 0.95, respectively. Clinical features (age, Hunt-Hess grade, etc.) were positively correlated with poor outcomes (P0.05).The levels of IL-1β, IL-18, and TNF-α in CSF were elevated in aSAH patients and were positively associated with cerebral edema and acute hydrocephalus. Our findings suggest that CSF inflammatory cytokines might be biomarkers to assess severity and predict outcomes.

The article discusses futures in housing development by applying the approaches from ‘future studies’ to design two explorative scenarios reflecting alternative strategies for achieving sustainable and just housing development. The main aim is to develop scenarios that can achieve a specific normative goal: a future housing development that is both environmentally sustainable and socially just. Two scenarios are built – ecological modernisation and degrowth – that reflect different degrees of societal change, ranging from conventional to radical. The scenarios are applied to the two selected cases of the Milan and Oslo regions, drawing on the statistics of the contextual housing system and the document analysis on planning and housing. We further discuss how the specific scenarios can take place and which challenges will be encountered.

// Henghui Cheng 1, 2 , Jin Xue 1, 2 , Shouhua Yang 3 , Yaobin Chen 1, 2 , Yu Wang 1, 2 , Yuanli Zhu 1, 2 , Xiaoyan Wang 1, 2 , Dong Kuang 1, 2 , Qiurong Ruan 1, 2 , Yaqi Duan 1, 2 and Guoping Wang 1, 2 1 Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China 2 Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China 3 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China Correspondence to: Yaqi Duan, email: yqduan@hust.edu.cn Guoping Wang, email: wanggp@hotmail.com Keywords: hepatocellular carcinoma, miR-497, miR-99a, IGF1R, mTOR Received: October 24, 2016 Accepted: April 29, 2017 Published: May 24, 2017 ABSTRACT Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3′-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR. Such inhibitory effect on tumor growth is reversed by application of IGF1 ((IGF1R ligand) or MHY1485 (mTOR agonist) in vitro . Furthermore, we found that simultaneous over-expression of both miR-497 and miR-99a exhibited much stronger inhibitory effects on tumor growth than their individual effect, which is still correlated with significantly stronger repression of IGF1R and mTOR. Overall, our results suggest that miR-497 and miR-99a both function as tumor-suppressive miRNAs by suppressing IGF1R/mTOR signaling pathway. The synergistic actions of these two miRNAs partly correlated with IGF1R and mTOR levels, which may represent new strategies for the molecular treatment of HCC.

// Jin-Xue He 1, * , Meng Wang 2, * , Xia-Juan Huan 1 , Chuan-Huizi Chen 1 , Shan-Shan Song 1 , Ying-Qing Wang 1 , Xue-Mei Liao 1 , Cun Tan 2 , Qian He 2 , Lin-Jiang Tong 1 , Yu-Ting Wang 1 , Xiao-Hua Li 1 , Yi Su 1 , Yan-Yan Shen 1 , Yi-Ming Sun 1 , Xin-Ying Yang 1 , Yi Chen 1 , Zhi-Wei Gao 3 , Xiao-Yan Chen 3 , Bing Xiong 2 , Xiu-Lian Lu 4 , Jian Ding 1 , Chun-Hao Yang 2 , Ze-Hong Miao 1 1 Division of Anti-Tumor Pharmacology and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, University of Chinese Academy of Sciences, Beijing 100049, China 2 Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, University of Chinese Academy of Sciences, Beijing 100049, China 3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 4 Cisen Pharmaceutical Co., LTD, Jining 272073, Shandong, China * These authors contributed equally to this work Correspondence to: Ze-Hong Miao, email: zhmiao@simm.ac.cn Chun-Hao Yang, email: chyang@simm.ac.cn Keywords: MPH, PARP inhibitor, homologous recombination, antitumor activity, synthetic lethality Received: April 01, 2016 Accepted: November 23, 2016 Published: December 01, 2016 ABSTRACT The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity. Notably, MPH displayed high water solubility (> 35 mg/ml) and potent PARP1/2 inhibition in a substrate-competitive manner. It reduced poly(ADP-ribose) (PAR) formation, enhanced γH2AX levels, induced G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells. Proof-of-concept studies confirmed the MPH-caused synthetic lethality. MPH showed potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide. A good relationship between the anticancer activity and the PARP inhibition of MPH suggested that PAR formation and γH2AX accumulation could serve as its pharmacodynamic biomarkers. Its high bioavailability (40%~100%) and high tissue distribution in both monkeys and rats were its most important pharmacokinetic features. Its average concentrations were 33-fold higher in the tissues than in the plasma in rats. Our work supports the further clinical development of MPH as a novel PARP1/2 inhibitor for cancer therapy.

Purpose In the practice of venture capital investment, the venture capital will not only claim the share of the enterprise’s future output, but also a certain amount of fixed income. The purpose of this paper is to examine the optimal contract which blends the variable ownership income and the fixed income theoretically so as to provide a keen insight into the venture capital practice. Design/methodology/approach This paper establishes an extended principal-agent model and researches on the design of optimal contract dominated by venture capital with double-sided moral hazard and information screening. Findings By establishing theoretical models, the main findings are: first, high-quality enterprise tends to relinquish less ownership but give more fixed return to the venture capital as compensation in order to obtain the venture capital financing; second, low-quality enterprise is willing to relinquish more ownership but give less fixed return to the venture capital for financing; third, due to the existence of double-sided moral hazard, neither of the venture capital and the enterprise will exert their best effort. Originality/value This paper furthers the application of principal-agent model in the field of venture capital investment and researches on the optimal contract, considering double-sided moral hazard and adverse selection at the same time originally.

Clinical studies have shown that obstructive sleep apnea (OSA) increases atherosclerosis risk. The inflammation, especially mediated by the macrophages via nuclear factor-κB (NF-κB), has been speculated to contribute to atherogenicity in OSA patients. Inhibitor of NF-κB kinase-β (IKKβ) is an essential element of the NF-κB pathway and is linked to atherosclerosis. We previously reported that atherosclerosis was accelerated in pulmonary artery (PA) but not in aorta when low-density lipoprotein receptor knockout ( Ldlr−/−) mice were exposed to intermittent hypoxia/hypercapnia (IHH), a surrogate for recurrent upper-airway obstruction. Therefore, we hypothesized that IKKβ-dependent NF-κB activation in monocytes and macrophages plays a role in IHH-induced PA atherosclerosis. To test this hypothesis, myeloid restricted IKKβ deletion ( IkkβΔMye) or control ( IkkβF/F) mice were crossed with Ldlr−/− mice to generate double-knockout mice. Then, the mice were exposed to IHH or room air (Air) on high-fat diet for 8 or 16 wk. Lesions of PA and aorta were examined in IkkβΔMye; Ldlr−/− and IkkβF/F; Ldlr−/− male mice under IHH vs. Air. The results revealed that IKKβ deletion abolished IHH-induced PA atherosclerosis after 8-wk exposure but not after 16-wk exposure (8 wk: IkkβF/F; Ldlr−/−, IHH 13.5 ± 1.4 vs. Air 5.7 ± 0.7%, P < 0.01; IkkβΔMye; Ldlr−/−, IHH 7.4 ± 1.9% vs. Air 4.6 ± 1.3%, P = 0.24). Both IKKβ deletion and IHH had no effects on atherosclerosis in the aorta. Our findings demonstrate that IKKβ-dependent NF-κB activity in myeloid-lineage cells plays a critical role in IHH-induced PA atherosclerosis at the early stage.

Based on a mixed-methods study of Norwegian second home users, this paper addresses travel distances, modes and carbon dioxide emissions from second home mobility, with a particular focus on reasons for choosing relevant modes of transportation to second home areas and while staying there. The questionnaire data show that the climate impacts are particularly high for trips to second homes located abroad, but due to their higher number, mobility when visiting domestic Norwegian second homes is also a sizeable source of CO2 emissions. Qualitative interviews with 18 participants illustrate important reasons why the car is often considered the default mode of travel when going to Norwegian second homes. These findings provide foundations for proposing land use and transport policies to reduce the climate impact of second home mobility.

Intelligence has been considered as the major challenge in promoting economic potential and production efficiency of precision agriculture. In order to apply advanced deep-learning technology to complete various agricultural tasks in online and offline ways, a large number of crop vision datasets with domain-specific annotation are urgently needed. To encourage further progress in challenging realistic agricultural conditions, we present the CropDeep species classification and detection dataset, consisting of 31,147 images with over 49,000 annotated instances from 31 different classes. In contrast to existing vision datasets, images were collected with different cameras and equipment in greenhouses, captured in a wide variety of situations. It features visually similar species and periodic changes with more representative annotations, which have supported a stronger benchmark for deep-learning-based classification and detection. To further verify the application prospect, we provide extensive baseline experiments using state-of-the-art deep-learning classification and detection models. Results show that current deep-learning-based methods achieve well performance in classification accuracy over 99%. While current deep-learning methods achieve only 92% detection accuracy, illustrating the difficulty of the dataset and improvement room of state-of-the-art deep-learning models when applied to crops production and management. Specifically, we suggest that the YOLOv3 network has good potential application in agricultural detection tasks.

Design and synthesis of new organic functional materials with improved performance or novel properties are of great importance in the field of optoelectronics. Azulene, as a non-alternant aromatic hydrocarbon, has attracted rising attention in the last few years. Different from most common aromatic hydrocarbons, azulene has unique characteristics, including large dipole moment, small gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). However, the design and synthesis of azulene-based functional materials are still facing several challenges. This review focuses on the recent development of organic functional materials employing azulene unit. The synthesis of various functionalized azulene derivatives is summarized and their applications in optoelectronics are discussed, with particular attention to the fields including nonlinear optics (NLO), organic field-effect transistors (OFETs), solar cells, and molecular devices.

The current study examined the cognitive mechanisms of distinguishing reality from fiction and distinguishing different fictional worlds. In Experiment 1, participants read sentences containing reality/fiction mismatch or fiction/fiction mismatch. Results showed that reality/fiction mismatch elicited a N400 effect and a late positivity relative to correct sentences, whereas fiction/fiction mismatch induced a N400 effect. Experiment 2 investigated the reality/fiction distinction after controlling personal relevance. Participants read sentences containing famous people or fictional characters with low personal relevance. Results indicated that reality/fiction mismatch elicited a late positivity in the middle and posterior sites, whereas the pure low relevance showed a late positivity in the posterior sites. The mechanisms under reality/fiction distinction, fiction/fiction distinction, and high/low relevance distinction are discussed.

Considering the demand of distributed power trading, a user-side power routing device topology is designed. The operation scenario of the device is divided into eight operation states, and the operation control strategy of the device system oriented to power trading is proposed for the eight operation states. In the process of power trading, grid-connected converters adopt Direct Power Control (DPC) to realize constant power trading. Super Capacitor (SC) adopt constant voltage control, Lithium battery adopt droop control, the Super Capacitor and the Lithium battery work together as the system bus voltage control unit. A simulation model is built on PSCAD/EMTDC platform, and two typical scenarios of power trading mode and non-trading mode are compared and analyzed. The simulation results verify the effectiveness of the proposed strategy.

Intestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders., Obstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2 (hypoxia) and high CO2 (hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2 and CO2 can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences. Here, we model human OSA and its cardiovascular consequence using Ldlr−/− mice fed a high-fat diet and exposed to intermittent hypoxia and hypercapnia (IHH). The gut microbiome and metabolome were characterized longitudinally (using 16S rRNA amplicon sequencing and untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) and seen to covary during IHH. Joint analysis of microbiome and metabolome data revealed marked compositional changes in both microbial (>10%, most remarkably in Clostridia) and molecular (>22%) species in the gut. Moreover, molecules that altered in abundance included microbe-dependent bile acids, enterolignans, and fatty acids, highlighting the impact of IHH on host-commensal organism cometabolism in the gut. Thus, we present the first evidence that IHH perturbs the gut microbiome functionally, setting the stage for understanding its involvement in cardiometabolic disorders. IMPORTANCE Intestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders.

As the best performing light emitting diodes (LEDs) are approaching the conventional limit of unity efficiency, a unique heat-pump operating mode of the devices has been proposed to address this problem, in which case lattice heat is pumped from the phonon field of the device into the incoherent photon field of emission at the expense of consuming zero-entropy electrical power. To better understand the potential of visible LEDs for further efficiency improvement in this mode, we present a thermodynamic framework that allows us to estimate the Carnot limit for their wall-plug efficiency (WPE) at different operating conditions. We find that the theoretical efficiency limit drops at higher light intensities but can still be well above 100% even at 10 W/cm^2. Ideally, realizing such high efficiency at useful output powers requires the device to possess an external quantum efficiency (EQE) close to unity. Here we are able to introduce dissipation into the thermodynamic model and thus determine a minimum EQE required for an LED to achieve unity WPE. In addition, the thermodynamic study for visible LEDs yields one surprising result. The first observation of above-unity WPE was on a heated mid-infrared (2.2 um) LED, and the subsequent demonstration at room temperature necessarily required a longer-wavelength 3.4 um device in order to realize sufficient carrier injection for measurable optical output. On the contrary, this thermodynamic analysis indicates that at useful optical powers – and hence useful cooling powers – visible LEDs of shorter wavelength are expected to show higher cooling at a lower current density.

Image-guided minimally invasive treatment (IG-MIT) has been widely used for local therapy of both benign and malignant tumors. However, precise needle targeting is a very important step in the minimally invasive treatment. Nowadays, minimally invasive treatment is usually performed with the guidance of the two-dimensional (2D) image. The tip of the puncture needle is difficult to place with precise positioning into the three-dimensional (3D) space of the tumor. This study was an experimental ex vivo study in porcine liver and heart samples with internal targets, focusing on the accuracy with the guidance of the real-time 3D imaging using a self-developed real-time ultrasonography and preoperative computed tomography (CT) fusion navigation system for minimal invasive tumor (liver tumor and uterine fibroid) therapy. There are thirty porcine liver samples and thirty porcine heart samples used in the experiments. The average weight of the porcine liver samples was 2216.8 g, and the average weight of the porcine heart samples was 510.5 g. We conducted statistical analysis of the experimental results obtained by five medical students and five interventional radiologists. The puncture precision of the needle placement under the guidance of 3D imaging was significantly higher than that of the other groups, and the assistant function is more obvious for medical students than that for interventional radiologists $$(p < 0.05)$$ . Assistant function of the US–CT fusion imaging is higher than that of the first group too $$(p

In order to distinguish the fatigue, drunk and normal driving effectively, sample entropy is introduced in this paper. An experiment was designed based on a driving simulator. 13 drivers were recruited to participate in the experiment. The steering wheel movement data in fatigue, drunk and normal state were collected. Sample entropy was used to analyze the characteristic of steering wheel movement under different radius curves in three driving states. The results show that the sample entropy in normal state is higher than that in fatigue state, while it is lower than that in drunk state. This indicates that sample entropy is feasible for distinguishing fatigue, drunk and normal driving.

With the development of the portable electronics industry, the need for more efficient power sources has been enlarged. Lithium-ion batteries are able to deliver high energy densities, high capacity and long cycle life at reasonable costs among competing energy storage technologies. The major goal of this paper is to introduce the promising Li-rich cathode material xLi2MnO3·(1-x) LiMO2(M=Ni, Co, Mn...), which owns enhanced energy and power density, high energy efficiency, superior rate capability and excellent cycling stability due to different modification methods.

Indoor localization is a very promising application for smartphone. Normally, we can obtain the relatively accurate location information from GPS in outdoor circumstances. However, GPS will be invalid for indoor applications, and we cannot achieve indoor localization with raw data of inertial measurement units (IMU) due to the drift of accelerometer in smartphone. In this paper, we proposed an estimation algorithm based on Kalman filtering to estimate the constant drift of accelerometer with the measurement data obtained outside. Then we can get the relatively accurate acceleration indoors due to removal of the drift and measurement noise. Afterwards, the position would be obtained by the numerical integration of acceleration. Finally, the verification of the proposed algorithm was given via simulation with favorable estimated drift and accurate location information.

LingLing Xue, YongBing Liu, HuiPing Xue, Jin Xue, KaiXuan Sun, LinFeng Wu, Ping Hou School of Nursing, YangZhou University, Yangzhou City, China Background: Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia. Uric acid is a water-soluble antioxidant found in the body. Many recent studies have found that uric acid plays an important role in cognitive impairment, although the effects of uric acid on MCI are not clear.Objective: The objective of this study was to explore the relationship between uric acid andMCI. Methods: Using a random sampling method, this study investigated 58 patients with MCI and 57 healthy elderly from January 2016 to November 2016. Demographic information was collected, the subjects were evaluated using the Mini Mental Status Examination (MMSE), and uric acid was measured in fasting venous blood.Results: A total of 57 (49.6%) participants are healthy and 58 (50.4%) participants had MCI. The uric acid level was significantly lower in the patients with MCI (292.28±63.71 µmol/L) than in the normal controls (322.49±78.70 µmol/L; P