REVIEW | doi:10.20944/preprints202201.0134.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: TRYCATs; MDD; MDE; Suicidal behavior; Kynurenine pathway
Online: 11 January 2022 (10:39:25 CET)
Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.
REVIEW | doi:10.20944/preprints201901.0285.v1
Subject: Engineering, Control & Systems Engineering Keywords: cyber physical systems; industry 4.0; MDE; lifetime verification & validation; dependability; correctness; flexibility; real-time self-adaptation, self-management; self-healing
Online: 29 January 2019 (04:45:47 CET)
Cyber Physical Systems (CPS) has been a popular research area in the last decade. The dependability of CPS is still a critical issue, and rare survey has been published in this domain. CPS is a dynamic complex system, which involves various multidisciplinary technologies. To avoid human error and to simplify management, self-management CPS (SCPS) is a wise choice. And to achieve dependable self-management, systematic solution is necessary to verify the design and to guarantee the safety of self-adaptation decision, as well as to maintain the health of SCPS. This survey first recalls the concepts of dependability, and proposes a generic environment-in-loop processing flow of self-management CPS, and then analyzes the error sources and challenges of self-management through the formal feedback flow. Focus on reducing the complexity, we first survey the self-adaptive architecture approaches and applied dependability means; then we introduce a hybrid multi-role self-adaptive architecture, and discuss the supporting technologies for dependable self-management at the architecture level. Focus on dependable environment-centered adaption, we investigate the verification and validation (V&V) methods for making safe self-adaptation decision and the solutions for processing decision dependably. For system-centered adaption, the comprehensive self-healing methods are summarized. Finally, we analyze the missing pieces of the technology puzzle and the future directions. In this survey, the technical trends for dependable CPS design and maintenance are discussed, an all-in-one solution is proposed to integrate these technologies and build a dependable organic SCPS. To the best of our knowledge, this is the first comprehensive survey on dependable SCPS building and evaluation.
ARTICLE | doi:10.20944/preprints201707.0044.v1
Subject: Engineering, Control & Systems Engineering Keywords: cyber physical systems; industry 4.0; MDE; hardware and software co-design; lifetime verification & validation; dependability; correctness; flexibility; self-management; self-adapting; self-healing
Online: 17 July 2017 (10:27:33 CEST)
Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.