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)

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)

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)

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)

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)

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)

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)

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)

Following the COVID-19 pandemic, online learning has become a new mode of learning that students must adapt to. However, the mechanisms by which students receive and grasp knowledge in the online learning mode remain unknown. Cognitive load theory offers instructions to students considering the knowledge of human cognition. Therefore, this study considers the CLT to explore the internal mechanism of learning under the online mode in an experimental study. We recruited 76 undergraduates and randomly assigned them to four groups in (...) which they will watch videos at four different kinds of speed. The study observed and analyzed how video playback speed affected students' learning and cognitive load to obtain the following results: Video playback speed significantly influenced the students' learning effect. The best effect was observed at the speed of 1.25× and 1.5×. The speed that affected the learning effect best differed according to the students' learning abilities. High-level group students performed best at the speed of 1.5×, whereas low-level group students performed best at the speed of 1.25×. The 1.5× speed showed significant differences in the learning effect by students' majors. This indicates that the cognitive load of liberal arts students increased greatly at this speed. A change in playback speed has a significant impact on the cognitive load. Accelerated playback speed increases the cognitive load of students. The highest learning effect is observed under medium cognitive load. (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)

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.

ObjectiveThis systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.MethodsThis systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the Participants, (...) Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.ResultsThe electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.ConclusionThe included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future. (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 the lexical kappa effect in 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 or phonological 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)

The characteristics of the meaning of inexpressible is given in the article. It is shown that in the Russian language semantics of inexpressible is represented as a binary functional-semantic category. It was determined that the nuances of semantics of inexpressible can be represented in the form of a gradational scale on which they are distributed within the opposition ‘complete inexpressibleness - complete expressibility‘. The components of the situation of inexpressibleness inherent the means of transference of the value of inexpressible are (...) described. It is shown that the definition of the components of situation of inexpressible contribute to the modeling of the field of semantics of inexpressible: what the concept of inexpressible means, in which situations semantics of inexpressible manifests itself; for whom this situation arises, how it is solved, can it be solved; by what means of language, speech and other semiotic systems it is expressed. It is determined that the situation of inexpressible includes seven components: the subject of speech inexpressibleness; an action that is impossible to express the statement; inexpressibility result of the process; objectivity of the situation described; reasons of inexpressibleness; the object of this situation; spatial area of the situation of inexpressibleness. It is shown that the central part of the functional-semantic field model components number 2, 3 and 4. The private values of the field of semantics of inexpressible were described for the first time. The definition of gradation nuances of inexpressibleness considering the paradigmatic and syntagmatic aspects of the study of the semantics were carried out for the first time. (shrink)

In the article the author’s solution of the inexpressibleness of the speech subject is given taking into account the asymmetry of the linguistic sign - signifying and signified - in relation to the elements of the functional-semantic category of the inexpressible. It was determined that the elements of the field of inexpressible are marked by the nomination of abstract vocabulary of three subclasses: 1) the most general feature, 2) the concept or term 3) the generic notions in relation to the (...) aspectual. On the other hand, the names, which are the surreal constructs of subject, in spite of an empty denotative value are not marked with an inexpressible, expressing a specific holistic image. From the object of speech, it can be said about a single inexpressibleness of the speech object signifying or signified, or the dual inexpressibleness - both signifying and signified. It is determined for the first time that under the dual inexpressibleness the categories denoting imaginary creatures in fiction or extraordinary beings, whose properties are impossible with nothing to relate, are actively being labeled with the elements of the field of inexpressible. The inexpressibleness of signified is conditioned by factors of external or internal linguistics. The factor of the internal linguistics is an aspect of existential inexpressibleness, the inexpressibleness of the subject of speech due to its otherness. This inexpressibleness is marked with the discursive pronouns usage. The factor of external linguistics is a competitive or psychophysical inexpressibleness due to the peculiarities of speech subject. The meaning of inexpressible is transmitted by interrogative sentences with a negative value, the particle if, indivisible combinations like ‘something untold‘. In situations with the meaning of a signifier, in which the speaker actually knows the meaning and only marks this sector as inexpressible - And she was an indescribable beauty - means of transferring of semantics of inexpressible finds centrifugal forces; from the field of inexpressible it migrates to the field of a very high quality concentration. This ‘migration‘ is being observed in the folk formulas, in the formulas of feeling expression. (shrink)

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)

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)

Compared with the large number of studies on reading of children with hearing loss in alphabetic languages, there are only a very limited number of studies on reading of Chinese-speaking children with HL. It remains unclear how phonological, orthographic, and semantic skills contribute to reading fluency of Chinese school-age children with HL. The present study explored this issue by examining the performances of children with HL on reading fluency and three linguistic skills compared with matched controls with normal hearing. Specifically, (...) twenty-eight children with HL and 28 chronological-age-matched children with NH were tested on word/sentence reading fluency, phonological awareness which was composed of onset/vowel/lexical tone awareness, orthographic knowledge, and semantic competence which comprised animal word identification, pseudo-homophone detection, and word segmentation. Results showed that children with HL lagged behind their peers with NH in WRF/SRF and most of the phonological, orthographic, and semantic subskills except onset awareness and pseudo-homophone detection. Furthermore, the significant contributors to WRF differed between the two groups with PA being the significant contributor in the children with NH while OK being the significant contributor in the children with HL. However, the significant contributor to SRF did not differ between the two groups with SC being the only significant contributor. These results revealed not only between-group differences but also similarities in the relative contributions of PA, OK, and SC to reading fluency at both word and sentence levels, which has practical implications for developing better training programs to improve reading for children with HL. (shrink)