cyber attack taxonomy for digital environment in nuclear power plants

With the development of digital instrumentation and control (I&C) devices, cyber security at nuclear power plants (NPPs) has become a hot issue. The Stuxnet, which destroyed Iran's uranium enrichment facility in 2010, suggests that NPPs could even lead to an accident involving the release of radioactive materials cyber-attacks.However, cyber security research on industrial control systems (ICSs) and supervisory control and data acquisition (SCADA) systems is relatively inadequate compared to information technology (IT) and further it is difficult to study cyber-attack taxonomy for NPPs considering the characteristics of ICSs. The advanced research of cyber-attack taxonomy does not reflect the architectural and inherent characteristics of NPPs and lacks a systematic countermeasure strategy.Therefore, it is necessary to more systematically check the consistency of operators and regulators related to cyber security, as in regulatory guide 5.71 (RG.5.71) and regulatory standard 015 (RS.015). For this reason, this paper attempts to suggest a template for cyber-attack taxonomy based on the characteristics of NPPs and exemplifies a specific cyber-attack case in the template. In addition, this paper proposes a systematic countermeasure strategy by matching the countermeasure with critical digital assets (CDAs). The cyber-attack cases investigated using the proposed cyber-attack taxonomy can be used as data for evaluation and validation of cyber security conformance for digital devices to be applied, and as effective prevention and mitigation for cyber-attacks of NPPs. Keywords: Cyber-attack taxonomy, Cyber security, Nuclear power plant, ICS, SCAD

An epigenetic blockade of cognitive functions in the neurodegenerating brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease [superscript 1]. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge [superscript 2]. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.Stanley Medical Research InstituteNational Institute of Neurological Disorders and Stroke (U.S.) (RO1NS078839)Swiss National Science FoundationBard Richmond (Fellowship)Simons FoundationTheodor und Ida Herzog-Egli Foundatio

An Epigenetic Blockade of Cognitive Functions in the Neurodegenerating Brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade

BNIP3-Dependent Mitophagy via PGC1α Promotes Cartilage Degradation

Since mitochondria are suggested to be important regulators in maintaining cartilage homeostasis, turnover of mitochondria through mitochondrial biogenesis and mitochondrial degradation may play an important role in the pathogenesis of osteoarthritis (OA). Here, we found that mitochondrial dysfunction is closely associated with OA pathogenesis and identified the peroxisome proliferator-activated receptor-gamma co-activator 1-alpha (PGC1α) as a potent regulator. The expression level of PGC1α was significantly decreased under OA conditions, and knockdown of PGC1α dramatically elevated the cartilage degradation by upregulating cartilage degrading enzymes and apoptotic cell death. Interestingly, the knockdown of PGC1α activated the parkin RBR E3 ubiquitin protein ligase (PRKN)-independent selective mitochondria autophagy (mitophagy) pathway through the upregulation of BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3). The overexpression of BNIP3 stimulated mitophagy and cartilage degradation by upregulating cartilage-degrading enzymes and chondrocyte death. We identified microRNA (miR)-126-5p as an upstream regulator for PGC1α and confirmed the direct binding between miR-126-5p and 3′ untranslated region (UTR) of PGC1α. An in vivo OA mouse model induced by the destabilization of medial meniscus (DMM) surgery, and the delivery of antago-miR-126 via intra-articular injection significantly decreased cartilage degradation. In sum, the loss of PGC1α in chondrocytes due to upregulation of miR-126-5p during OA pathogenesis resulted in the activation of PRKN-independent mitophagy through the upregulation of BNIP3 and stimulated cartilage degradation and apoptotic death of chondrocytes. Therefore, the regulation of PGC1α:BNIP3 mitophagy axis could be of therapeutic benefit to cartilage-degrading diseases

Activity Prediction Based on Deep Learning Techniques

Studies on real-time PM2.5 concentrations per activity in microenvironments are gaining a lot of attention due to their considerable impact on health. These studies usually assume that information about human activity patterns in certain environments is known beforehand. However, if a person’s activity pattern can be inferred reversely using environmental information, it can be easier to access the levels of PM2.5 concentration that affect human health. This study collected the actual data necessary for this purpose and designed a deep learning algorithm that can infer human activity patterns reversely using the collected dataset. The dataset was collected based on a realistic scenario, which includes activity patterns in both indoor and outdoor environments. The deep learning models used include the well-known multilayer perception (MLP) model and a long short-term memory (LSTM) model. The performance of the designed deep learning algorithm was evaluated using training and test data. Simulation results showed that the LSTM model has a higher average test accuracy of more than 15% compared to the MLP model, and overall, we were able to achieve high accuracy of over 90% on average

Exercise-induced myokines in health and metabolic diseases

Skeletal muscle has been emerging as a research field since the past 2 decades. Contraction of a muscle, which acts as a secretory organ, stimulates production, secretion, and expression of cytokines or other muscle fiber-derived peptides, i.e., myokines. Exercise-induced myokines influence crosstalk between different organs in an autocrine, endocrine, or paracrine fashion. Myokines are recently recognized as potential candidates for treating metabolic diseases through their ability to stimulate AMP-activated protein kinase signaling, increase glucose uptake, and improve lipolysis. Myokines may have positive effects on metabolic disorders, type 2 diabetes, or obesity. Numerous studies on myokines suggested that myokines offer a potential treatment option for preventing metabolic diseases. This review summarizes the current understanding of the positive effects of exercise-induced myokines, such as interleukin-15, brain-derived neurotrophic factor, leukemia inhibitory factor, irisin, fibroblast growth factor 21, and secreted protein acidic and rich in cysteine, on metabolic diseases