Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Playing an important role in electromechanical systems, hydraulic servo system is crucial to mechanical systems like engineering machinery, metallurgical machinery, ships, and other equipment. Fault diagnosis based on monitoring and sensory signals plays an important role in avoiding catastrophic accidents and enormous economic losses. This study presents a fault diagnosis scheme for hydraulic servo system using compressed random subspace based ReliefF method. From the point of view of feature selection, the scheme utilizes CRSR method to determine the most stable feature (...) combination that contains the most adequate information simultaneously. Based on the feature selection structure of ReliefF, CRSR employs feature integration rules in the compressed domain. Meanwhile, CRSR substitutes information entropy and fuzzy membership for traditional distance measurement index. The proposed CRSR method is able to enhance the robustness of the feature information against interference while selecting the feature combination with balanced information expressing ability. To demonstrate the effectiveness of the proposed CRSR method, a hydraulic servo system joint simulation model is constructed by HyPneu and Simulink, and three fault modes are injected to generate the validation data. (shrink)

Irresponsible research practices damaging the value of science has been an increasing concern among researchers, but previous work failed to estimate the prevalence of all forms of irresponsible research behavior. Additionally, these analyses have not included articles published in the last decade from 2011 to 2020. This meta-analysis provides an updated meta-analysis that calculates the pooled estimates of research misconduct and questionable research practices, and explores the factors associated with the prevalence of these issues. The estimates, committing RM concern at (...) least 1 of FFP and QRPs concern 1 or more QRPs, were 2.9% and 12.5%, respectively. In addition, 15.5% of researchers witnessed others who had committed at least 1 RM, while 39.7% were aware of others who had used at least 1 QRP. The results document that response proportion, limited recall period, career level, disciplinary background and locations all affect significantly the prevalence of these issues. This meta-analysis addresses a gap in existing meta-analyses and estimates the prevalence of all forms of RM and QRPs, thus providing a better understanding of irresponsible research behaviors. (shrink)

Patients requiring deep brain stimulation due to intracerebral metallic foreign substances have not been reported elsewhere in the world. Additionally, the long-term effects of metallic foreign bodies on deep brain stimulation are unknown. A 79-year-old man with a 5-year history of Parkinson's disease reported that, 40 years ago, while playing with a pistol, a metallic bullet was accidentally discharged into the left brain through the edge of the left eye, causing no discomfort other than blurry vision in the left eye. (...) DBS was performed due to the short duration of efficacy for oral medication. Because the bullet was on the left subthalamic nucleus electrode trajectory and the patient's right limb was primarily stiff, the patient received globus pallidus interna -DBS implantation in the left hemisphere and STN-DBS implantation in the right hemisphere. During a 6-month postoperative follow-up, the patient's PD symptoms were effectively managed with no noticeable discomfort. (shrink)

Public value facilitates the democratization of public policy making, it should be the common-sense and bottom-line for policymakers. However, it has not been paid enough attention by the practical and theoretical circles. How to realize the transformation from individual value to public value and make public policies be in line with citizens’ preferences, is vital for the democratic politics. How individual value becomes public value in the agenda-setting stage during the policy-making process? What are the key influencing factors? Using the (...) case of Yangzhou Chemical Co. Youjia Program and interview data, this paper studies the mechanisms that could make individual value be transformed to public value through deeply observing and measuring individuals’ attitudes, demands, motivations, beliefs, and preferences. We argue that (1) public value is an essential foundation for agenda setting and guidance to policy making, whereas individual value cannot naturally substitute value orientation in the public sphere. (2) Transferring individual value to public value can reduce divergence appearing in the subsequent stage in policy activities. (3) Factors that can influence this transformation are policy subjects, relations, rule and expression channels with various determinants and conditions. (4) Public value can terminate irrational and unreasonable policies or drag the policy issues back into the agenda-setting stage. This paper provides unique insights into why individual citizens enter the public sphere to take public actions so that the Chinese government can recognize additional public opinions, which makes cooperative governance be realized. (shrink)

The early decades of the last century saw European philosophical thought becoming increasingly interested in the sociological extension of the idea of law. From the viewpoint of the sociology of law, law is formed in the process of social interactions and is not sanctioned by the state. Sergey Hessen and Georges Gurvitch base their conceptions of social law on the sociology of law in the 1920s and 1930s. They start a polemic in the pages of the journal Sovremenniye zapiski. Although (...) they differ radically in their definitions of the status of the state they concur in defining society as a set of social institutions and communities existing as instruments for expressing personal freedom. The social regulations they propose are already legal situations. Hessen and Gurvitch believe that the individual can fully exercise his/her freedom only in conditions of such legal pluralism. However, the concept of legal pluralism involves an inherent problem of preserving social unity: why is it that society does not fall into a range of autonomous social entities, each offering the individual its own legal order for actualising freedom? To solve this problem the philosophers use the concept of “the general will”. General will is an instrument of correlation between individual freedom and the development of society and culture as a whole. The object of philosophical dispute is how the general will is formed: 1) in the process of social self-organisation according to Gurvitch; 2) in the operation of the suprafunctional organisation according to Hessen. The difference in the grounding of the general will leads to a difference in the concepts of social unity: 1) sobornost according to Gurvitch and 2) solidarity according to Hessen. Analysis of the dispute between Gurvitch and Hessen brings out not only the differences in the interpretation of social unity but also the fundamental problems with the conceptions of social law. (shrink)

We analyze and study the tracking of nonrigid complex targets of sports video based on mean shift fusion color histogram algorithm. A simple and controllable 3D template generation method based on monocular video sequences is constructed, which is used as a preprocessing stage of dynamic target 3D reconstruction algorithm to achieve the construction of templates for a variety of complex objects, such as human faces and human hands, broadening the use of the reconstruction method. This stage requires video sequences of (...) rigid moving target objects or sets of target images taken from different angles as input. First, the standard rigid body method of Visuals is used to obtain the external camera parameters of the sequence frames as well as the sparse feature point reconstruction data, and the algorithm has high accuracy and robustness. Then, a dense depth map is computed for each input image frame by the Multi-View Stereo algorithm. The depth reconstruction with a too high resolution not only increases the processing time significantly but also generates more noise, so the resolution of the depth map is controlled by parameters. The multiple hypothesis target tracking algorithms are used to track multiple targets, while the chunking feature is used to solve the problem of mutual occlusion and adhesion between targets. After finishing the matching, the target and background models are updated online separately to ensure the validity of the target and background models. Our results of nonrigid complex target tracking by mean shift fusion color histogram algorithm for sports video improve the accuracy by about 8% compared to other studies. The proposed tracking method based on the mean shift algorithm and color histogram algorithm can not only estimate the position of the target effectively but also depict the shape of the target well, which solves the problem that the nonrigid targets in sports video have complicated shapes and are not easy to track. An example is given to demonstrate the effectiveness and adaptiveness of the applied method. (shrink)

Searching is one of the most fundamental operations in many complex systems. However, the complexity of the search process would increase dramatically in high-dimensional space. K-dimensional tree, as a classical data structure, has been widely used in high-dimensional vital data search. However, at present, common methods proposed for KD tree construction are either unstable or time-consuming. This paper proposed a new algorithm to construct a balanced KD tree based on presorted results. Compared with previous similar method, the new algorithm could (...) reduce the complexity of the construction process from O level to O level, where K is the number of dimensions and N is the number of data. In addition, with the help of presorted results, the performance of the new method is no longer subject to the initial conditions, which expands the application scope of KD tree. (shrink)

The intertemporal stability of research and development investment is a key issue in successfully promoting the continuation of innovation activities under high uncertainty in entrepreneurship. R&D smoothing helps firms to navigate the uncertainties of the external environment and maintain the stability of their investments in innovation. Chief executive officers are the most important decision-makers in firms' strategic planning. However, overconfident CEOs may overlook the importance of their firms' strategic actions on innovative activities. Drawing on upper echelons theory, this paper examines (...) how CEO overconfidence affects firms' R&D smoothing. Using a sample of firms listed in China's Growth Enterprises Market between 2013 and 2020, this study finds that CEO overconfidence has a significant negative impact on R&D smoothing. Furthermore, our findings reveal that firms' internal control quality and institutional investor monitoring can mitigate the negative association between CEO overconfidence and R&D smoothing. Our findings provide new insights into the micro-level theoretical explanations for R&D smoothing and offer practical implications for technology-based entrepreneurial firms. (shrink)

The aim of this paper is to explore the role of ethical climate on the relationship between the paternalistic leadership and team identification at the team level. In contrast to the prior studies which tended to focus on ethical climate as a whole dimension, this paper further classified the domain of construct into the categories of egoism, benevolence, and principle using a sample from 143 teams in Mainland China and Taiwan. Hierarchical regression results showed that the average paternalistic leadership had (...) a significant impact on the team identification at the team level. Moreover, the results indicated that the ethical climate of benevolence fully mediated while the ethical climate of egoism partially mediated the relationship between authoritarian leadership and team identification. Also, the ethical climates of benevolence and principle had a partial mediating effect on the relationship between benevolent leadership and team identification as well as moral leadership and team identification, respectively, but the ethical climate of egoism did not play a significant role. The major findings, theoretical contributions, practical implications, and the limitations were discussed. (shrink)

The present research explored differences in gift evaluation between gift givers and receivers. Three studies were conducted to test how the pricing influenced the gift evaluations of givers and receivers, and whether the price-quality and price-monetary sacrifice inferences were the underlying mechanisms. The results showed that: givers evaluated high-priced gifts as better than low-priced gifts, whereas receivers evaluated low-priced gifts as better than high-priced gifts; price-quality inference mediated the effect of pricing on gift evaluations, but only for givers. Furthermore, the (...) effect of pricing on gift evaluation was moderated by the gift type: givers evaluated the high-priced gift as better only for the desirable gift ; receivers evaluated the low-priced gift as better only for the feasible gift. The results demonstrate the effect of pricing on gift evaluation and could contribute to understanding the differences between givers’ and receivers’ perception of what a “good gift” is, and the underlying psychological mechanisms. (shrink)

The aim of this study is to develop an integrative model linking the effect of authoritarian leadership and differential leadership on employee turnover intention, and further explore the moderating role of the in-group/out-group on the above-mentioned relationships. We collected a sample of 624 supervisor–subordinate dyads from 87 teams in Mainland China and Taiwan. We find that, at the individual level, authoritarian leadership is positively related with employee turnover intention, and the relationship will be enhanced especially when the subordinate is an (...) in-group member. Through hierarchical linear modeling analysis, we find a negative relationship between differential leadership and employee turnover intention, significantly moderated by the within-team mean degree and the within-team variance degree of in-group/out-group. Contributions, limitations, and future research directions are discussed. (shrink)

The kappa effect is a well-reported phenomenon in which spatial distance between discrete stimuli affects the perception of temporal distance demarcated by the corresponding stimuli. Here, we report a new phenomenon that we propose to designate as thelexical kappa effectin which word distance, a non-magnitude relationship of discrete stimuli that exists in the lexical space of the mental lexicon, affects the perception of temporal distance. A temporal bisection task was used to assess the subjective perception of the time interval demarcated (...) by two successively presented words. Word distance was manipulated by varying the semantic (Experiment 1) or phonological (Experiment 2) similarity between the two words. Results showed that the temporal distance between the two words was perceived to be shorter when the corresponding two words were lexically closer. We explain this effect within the internal clock framework by assuming faster detection of the word that terminated timing when it is preceded by a semantically or phonologically similar word. (shrink)

This study chooses Chinese athletes as the research object and constructs the overall network of its social support network and discussion network. From the micro-, meso-, and macrolevels of the social network structure, the structure and characteristics of the athlete’s overall social network are analyzed. Through research, we found that there is embeddedness, that is, the relevance, between society support networks, between society discussion networks, and between society support networks and society discussion networks. At the same time, in the athletes’ (...) social support network and social discussion network, some athletes have no contact with other players; they have no “power” in the group as well, so it is difficult to obtain network resources. We also found that there are small-world characteristics in the social network of Chinese professional athletes. The above findings will provide a deeper understanding of the peculiarities of athlete groups and have certain practical significance for improving athletes’ daily training and life management conditions. (shrink)

Spermiogenesis is an important physiological process of mammalian fertilization. The germ cells are susceptible to the harmful effects of either psychological or physiological stress, which could induce male infertility. Our previous studies have found that chronic psychological stress could decrease sexual motivation. However, molecular mechanisms underlying male reproductive toxicity induced by chronic stress remain elusive. Recently, autophagy is proven to be involved in regulating the survival of germ cells, which is related to apoptosis. Herein, we established a chronic psychological stress (...) model and a chronic pain model (physiological stressor) to explore the roles of autophagy in germ cells. Thirty-two male Sprague-Dawley rats were randomly divided into four groups, including the control group, the chronic psychological stress group, the SNI-sham group, and the chronic pain stress group. After exposure to stress for 35 days, open field test and the unconditioned sexual motivation test were performed. Following the behavioral experiment, autophagy in the rat testis was detected by Western blot and immunohistochemistry. We found both chronic psychological stress and chronic pain stress reduced total travel distance, the frequency of central crossing and increased the sensitivity to mechanical pain. While chronic psychological stress, but not the chronic pain stress declined sexual motivation. Chronic psychological stress prompt the expression of LC3-II with the decreased expression of p62, indicating that chronic psychological stress induced autophagy in rat testis. However, there was no significant difference between the expression of LC3-II and p62 in male rats under chronic pain stress. Therefore, chronic psychological stress and chronic pain stress have common behavior changes, but due to its unpredictability, chronic psychological stress leads to a decline in sexual motivation in male rats and induced the autophagy in testicular tissues. (shrink)

Barzykowski and Moulin argue both involuntary autobiographical memories and déjà vu experiences rely on the same involuntary memory retrieval processes but their underlying neurological basis remains unclear. We propose spontaneous neural replay in the default mode network (DMN) and hippocampus as the basis for involuntary autobiographical memories, whereas for déjà vu experiences such transient activation is limited to the DMN.

Research has indicated that microRNAs (miRNAs), a special class of non-coding RNAs (ncRNAs), can perform important roles in different biological and pathological processes. miRNAs’ functions are realized by regulating their respective target genes (targets). It is thus critical to identify and analyze miRNA-target interactions for a better understanding and delineation of miRNAs’ functions. However, conventional knowledge discovery and acquisition methods have many limitations. Fortunately, semantic technologies that are based on domain ontologies can render great assistance in this regard. In our (...) previous investigations, we developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), to provide the community with common data elements and data exchange standards in the miRNA research. This paper describes (1) our continuing efforts in the OMIT ontology development and (2) the application of the OMIT to enable a semantic approach for knowledge capture of miRNA-target interactions. (shrink)

Several years ago, in quantum mechanics, Davies proposed a method to calculate particle’s traveling time with the phase difference of wave function. The method is convenient for calculating the sojourn time inside a potential step and the tunneling time through a potential hill. We extend Davies’ non-relativistic calculation to relativistic quantum mechanics, with and without particle-antiparticle creation, using Klein–Gordon equation and Dirac Equation, for different forms of energy-momentum relation. The extension is successful only when the particle and antiparticle creation/annihilation effect (...) is negligible. (shrink)

Large-scale sequencing tests, including whole-exome and whole-genome sequencing, are rapidly moving into clinical use. Sequencing is already being used clinically to identify therapeutic opportunities for cancer patients who have run out of conventional treatment options, to help diagnose children with puzzling neurodevelopmental conditions, and to clarify appropriate drug choices and dosing in individuals. To evaluate and support clinical applications of these technologies, the National Human Genome Research Institute and National Cancer Institute have funded studies on clinical and research sequencing under (...) the Clinical Sequencing Exploratory Research program as well as studies on return of results. Most of these studies use sequencing in real-world clinical settings and collect data on both the application of sequencing and the impact of receiving genomic findings on study participants. They are occurring in the context of controversy over how to obtain consent for exome and genome sequencing. (shrink)

“Welcome Back Tourism” is an important marketing strategy to help overseas Tourism destinations quickly recover from the crisis and enhance their core competitiveness. How to translate the memorability of tourists to revisit intention is the core key to open “Welcome Back Tourism.” This study takes local residents in Guangzhou, Shenzhen and Foshan as the research objects, and tries to explore the influence relationship between memorability of a previous travel experience, nostalgia, destination attachment and revisit intention. The results of 291 valid (...) data showed that memorability of a previous travel experience had positive influence on revisit intention; Nostalgia has a positive effect on destination attachment. Nostalgia and destination attachment play a mediating role in the influence of memorability of a previous travel experience on revisit intention. The contributions and management Recommendations of these findings are discussed. (shrink)

本书分为唯物史观研究的一般问题、坚持唯物史的基本原理、社会及其进步问题、科学发展观与唯物史观的创新等七部分。.

At almost every election, Americans are inclined to say that this is the most consequential election in American history. 2020 is no exception. However, what is particularly remarkable about the No...