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This study proposes a scheme to identify insider threats in nuclear facilities through the detection of malicious intentions of potential insiders using subject-wise classification. Based on electroencephalography (EEG) signals, a classification model was developed to identify whether a subject has a malicious intention under scenarios of being forced to become an insider threat. The model also distinguishes insider threat scenarios from everyday conflict scenarios. To support model development, 21-channel EEG signals were measured on 25 healthy subjects, and sets of features were extracted from the time, time–frequency, frequency and nonlinear domains. To select the best use of the available features, automatic selection was performed by random-forest-based algorithms. The k-nearest neighbor, support vector machine with radial kernel, naïve Bayes, and multilayer perceptron algorithms were applied for the classification. By using EEG signals obtained while contemplating becoming an insider threat, the subject-wise model identified malicious intentions with 78.57% accuracy. The model also distinguished insider threat scenarios from everyday conflict scenarios with 93.47% accuracy. These findings could be utilized to support the development of insider threat mitigation systems along with existing trustworthiness assessments in the nuclear industry.

What explains South Korean public opinion on nuclear weapons development? Despite the US security commitment, most South Koreans consistently support independent nuclear weapons development. To solve this puzzle, we investigate the mechanisms of security threat and security commitment under which individuals develop their opinion on nuclear proliferation. An original survey of 1,988 South Korean adults shows empirically supported correlates of South Korean public opinion on nuclear proliferation. Public support for proliferation is largely shaped by external security threats: nuclear threats from North Korea and China, but also the latent nuclear superiority of Japan. Public opposition to proliferation is fostered by the perceived credibility of the US security commitment, but not by its perceived effectiveness. The results provide insights into South Korean public opinion on nuclear proliferation and can inform the design of a nonproliferation policy tailored to South Korea.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy. The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.

RationaleIdiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose.MethodsWe explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung.ResultsWe provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF.ConclusionsOur data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-of-mechanism trial of this agent is currently underway.Trial registration numberNCT01725139, pre-clinical.

What factors constrain the arrangement of the multiple fields of a place cell? By modeling place cells as perceptrons that act on multiscale periodic grid-cell inputs, we analytically enumerate a place cell’s repertoire – how many field arrangements it can realize without external cues while its grid inputs are unique – and derive its capacity – the spatial range over which it can achieve any field arrangement. We show that the repertoire is very large and relatively noise-robust. However, the repertoire is a vanishing fraction of all arrangements, while capacity scales only as the sum of the grid periods so field arrangements are constrained over larger distances. Thus, grid-driven place field arrangements define a large response scaffold that is strongly constrained by its structured inputs. Finally, we show that altering grid-place weights to generate an arbitrary new place field strongly affects existing arrangements, which could explain the volatility of the place code.

We propose a high-dimensional generalisation of the standard Klein bottle extending beyond those considered previously. We address the problem of generating continuous scalar fields (distributions) and dynamical systems (flows) on such state spaces, which can provide a rich source of examples for future investigations. We consider a class of high-dimensional dynamical systems that model distributed information processing within the human cortex, which may be capable of exhibiting some Klein bottle symmetries. We deploy topological data analytic methods in order to analyse their resulting dynamical behaviour and suggesting future challenges.

In recent decades, the nuclear export market has observed a marked shift of demand from traditional customers in the Western world to Asia. The lack of projects in the United States, the delay in the French construction of advanced reactors, and the Fukushima accident in Japan have also led to the declining export capabilities of their companies. In contrast, Russia has gained numerous contracts, and China will likely become another major exporter. In this paper, the evolution of the market was examined from both the supply and demand sides with issues including the more concentrated and uncertain market, the lack of full participation by emerging suppliers to the nonproliferation regime, and the lesser governance capabilities of the newcomers. Addressing these issues, a range of policy suggestions was made, including the reinforcement of market shares of Western suppliers, the encouragement of newcomers to adhere to international norms, and a better safeguards contribution scheme.

In the main control room (MCR) of a nuclear power plant (NPP), the quality of an operator's performance can depend on their level of attention to the task. Insufficient operator attention accounted for more than 26% of the total causes of human errors and is the highest category for errors. It is therefore necessary to check whether operators are sufficiently attentive either as supervisors or peers during reactor operation. Recently, digital control technologies have been introduced to the operating environment of an NPP MCR. These upgrades are expected to enhance plant and operator performance. At the same time, because personal computers are used in the advanced MCR, the operators perform more cognitive works than physical work. However, operators may not consciously check fellow operators' attention in this environment indicating potentially higher importance of the role of operator attention. Therefore, remote measurement of an operator's attention in real time would be a useful tool, providing feedback to supervisors. The objective of this study is to investigate the development of quantitative indicators that can identify an operator's attention, to diagnose or detect a lack of operator attention thus preventing potential human errors in advanced MCRs. To establish a robust baseline of operator attention, this study used two of the widely used biosignals: electroencephalography (EEG) and eye movement. We designed an experiment to collect EEG and eye movements of the subjects who were monitoring and diagnosing nuclear operator safety-relevant tasks. There was a statistically significant difference between biosignals with and without appropriate attention. Furthermore, an average classification accuracy of about 90% was obtained by the k-nearest neighbors and support vector machine classifiers with a few EEG and eye movements features. Potential applications of EEG and eye movement measures in monitoring and diagnosis tasks in an NPP MCR are also discussed.

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia.

The Hong Kong Government developed the Reference Framework for Preventive Care for Older Adults (RF) to provide evidence-based recommendations for preventive care in the primary care setting. However, no study has systematically evaluated the adoption and awareness of this framework among primary care physicians (PCPs). This study aimed to explore PCPs' perceptions of the RF and identify barriers and facilitators to its adoption in primary care settings. This cross-sectional qualitative study involved interviews with 40 PCPs in Hong Kong to assess their views on the RF's adoption and implementation. The Consolidated Framework for Implementation Research (CFIR) was used to guide the analysis, focusing on five domains: intervention characteristics, outer setting, inner setting, individual characteristics, and implementation process. Relative advantage (65%, n = 26), innovation design (45%, n = 18), and access to knowledge and information (70%, n = 28) were the facilitators that mostly discussed by interviewee. By contrast, interviewees also raised concerns regarding policy and legal (n=29, 73%) and availability of resources (n=29, 73%) in the implementation of the RF. In general, participants acknowledged the RF's evidence-based foundation and comprehensive design, appreciating its potential to improve care for older adults. However, barriers included the complexity and limited personalization of the RF, competing clinical priorities, time constraints, and resource limitations. Government support and policy initiatives facilitated engagement, but clearer integration into existing workflows and stronger promotion were needed. Tailored updates, user feedback, and technological enhancements were seen as essential for improving the RF's usability and ensuring its relevance in clinical practice. This study highlights that while the RF has potential to improve preventive care in Hong Kong's primary care setting, its adoption is constrained by systemic, organizational, and individual barriers. To ensure its successful integration, flexible implementation, institutional support, tailored incentives, and enhanced clinician and patient engagement are essential. These findings offer practical implications for policymakers and healthcare practitioners to refine and promote the RF in routine consultations, and underscore the need for future research to test theory-informed implementation strategies. Furthermore, this study offered novel contributions to the CFIR literatures in systematically investigate physician perspectives on RF for the older adult population within the distinct socio-cultural and structural context of Hong Kong, COVID-19 pandemic impact to the current healthcare system and actionable implementation strategies for Asian populations. Applying the findings from this study, the CFIR-ERIC Matching Tool could be used to address the specific barriers identified in this study and improving implementation outcomes across various healthcare settings.