| 1. |
- Andersson, David A., et al.
(author)
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TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol
- 2011
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 2
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Journal article (peer-reviewed)abstract
- TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1(-/-) mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, activate mouse and human TRPA1. These metabolites also activate native TRPA1 and, as a consequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons. The N-acetyl-p-benzoquinoneimine metabolite l-cysteinyl-S-acetaminophen was detected in the mouse spinal cord after systemic acetaminophen administration. In the hot-plate test, intrathecal administration of N-acetyl-p-benzoquinoneimine, p-benzoquinone and the electrophilic TRPA1 activator cinnamaldehyde produced antinociception that was lost in Trpa1(-/-) mice. Intrathecal injection of a non-electrophilic cannabinoid, Delta(9)-tetrahydrocannabiorcol, also produced TRPA1-dependent antinociception in this test. Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain.
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| 2. |
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| 3. |
- Hagey, Daniel W., et al.
(author)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Journal article (peer-reviewed)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 4. |
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| 5. |
- Alenmyr, Lisa, et al.
(author)
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Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.
- 2012
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In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 110, s. 264-268
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Journal article (peer-reviewed)abstract
- Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.
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| 6. |
- Alizadeh, Morteza, 1987-, et al.
(author)
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A Survey of Secure Internet of Things in Relation to Blockchain
- 2020
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In: Journal of Internet Services and Information Security (JISIS). - Seoul, Republic of Korea : Innovative Information Science & Technology Research Group (ISYOU). - 2182-2069 .- 2182-2077. ; 10:3, s. 47-75
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Journal article (peer-reviewed)abstract
- Distributed ledgers and blockchain technologies can improve system security and trustworthiness by providing immutable replicated histories of data. Blockchain is a linked list of blocks containing digitally signed transactions, a cryptographic hash of the previous block, and a timestamp stored in a decentralized and distributed network. The Internet of Things (IoT) is one of the application domains in which security based on blockchain is discussed. In this article, we review the structure and architectures of distributed IoT systems and explain the motivations, challenges, and needs of blockchain to secure such systems. However, there are substantial threats and attacks to blockchain that must be understood, as well as suitable approaches to mitigate them. We, therefore, survey the most common attacks to blockchain systems and the solutions to mitigate them, with the objective of assessing how malicious these attacks are in the IoT context.
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| 7. |
- Alizadeh, Morteza, 1987-
(author)
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Architectural Aspects of Identification in Decentralized Systems
- 2024
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Doctoral thesis (other academic/artistic)abstract
- High-level systems need identification techniques, where higher security and scalability are considered requirements. Identification plays a significant role in systems where smart electronic devices increase in zero trust and open environments like decentralized systems. Also, decentralization has emerged as one of the most exciting domains in recent years, again after the first Internet was invented. Besides, decentralization in identification systems has gained popularity worldwide since cryptocurrencies became part of businesses. Distributed Ledger Technology (DLT) and Distributed Hash Tables (DHT) can be appropriate decentralized solutions that improve identification to be much more secure, scalable, and trustworthy.The decentralized nature of DLT and DHT ensures no single point of failure, making them highly resilient to attacks. Blockchain as a DLT solution can help devices communicate with each other securely and trustably by storing an immutable history of transactions, providing an additional layer of security to identification systems. DHT senable applications to keep files and information immutable in a decentralized manner. DHTs ensure that the data is replicated across multiple nodes, making it highly resilient to data loss. Moreover, mitigating high storage costs without memory limitations is the target of these technologies. In this context, a decentralized system paradigm that combines systems with DLT and DHTs can be highly beneficial.This thesis argues for such a paradigm, and the contributions include introducing the term decentralized networks and architectures and demonstrating the feasibility of using blockchain as a DLT solution in real-world scenarios. These scenarios can be applied to the Internet of Things (IoT) or other Peer to Peer networked systems. We explore different architectures in various systems and analyze the interaction in blockchain. This thesis contributes to developing decentralized identification systems that provide users’ trust in an open environment. It presents the challenges associated with decentralized identification, including registry and storage issues, and proposes solutions using DLT and DHT. The immutability of DLT and DHTs provides fast and secure solutions for decentralized identification systems. In particular, we show that a DHT-based architecture is feasible to maintain decentralization while avoiding memory constraints. However, there is still room for improvement in terms of performance. Our investigation shows that combining DHTs with blockchain in decentralized identifiers improves performance.By concealing blocks in the private blockchain, we show that query performance is better than other DHT and public blockchain-based solutions without concealed information. Moreover, our results show that DHT performs better than the public blockchain for scenarios with many records.These findings highlight the importance of selecting the appropriate technology for decentralized identification systems, considering the specific use case and the number of records to be stored.We also consider different decentralized identification systems and platforms built based on the recommendation of W3C Decentralized Identifiers (DIDs). We found low-efficiency issues using this technology, resulting from leveraging public DLT in the data registry part of DIDs. That model has searching time problems if the DLT grows. Finally, this thesis helps to analyze these issues and find better solutions. By choosing the right technology, we can ensure that decentralized identifiers are efficient, secure, and scalable, which enables users to trust them in an open environment.
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| 8. |
- Alizadeh, Morteza, 1987-, et al.
(author)
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Comparative Analysis of Decentralized Identity Approaches
- 2022
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In: IEEE Access. - : IEEE. - 2169-3536. ; 10, s. 92273-92283
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Journal article (peer-reviewed)abstract
- Decentralization is essential when trust and performance must not depend on a single organization. Distributed Ledger Technologies (DLTs) and Decentralized Hash Tables (DHTs) are examples where the DLT is useful for transactional events, and the DHT is useful for large-scale data storage. The combination of these two technologies can meet many challenges. The blockchain is a DLT with immutable history protected by cryptographic signatures in data blocks. Identification is an essential issue traditionally provided by centralized trust anchors. Self-sovereign identities (SSIs) are proposed decentralized models where users can control and manage their identities with the help of DHT. However, slowness is a challenge among decentralized identification systems because of many connections and requests among participants. In this article, we focus on decentralized identification by DLT and DHT, where users can control their information and store biometrics. We survey some existing alternatives and address the performance challenge by comparing different decentralized identification technologies based on execution time and throughput. We show that the DHT and machine learning model (BioIPFS) performs better than other solutions such as uPort, ShoCard, and BBID.
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| 9. |
- Alizadeh, Morteza, 1987-, et al.
(author)
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Decentralized Identifiers using Distributed Ledger Technologies
- 2023
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In: 2023 IEEE Asia-Pacific Conference on Computer Science and Data Engineering (CSDE). - : IEEE.
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Conference paper (peer-reviewed)abstract
- Decentralized identification is an interesting topic for Internet-based systems. Although the use of centralized systems for identification is prevalent, there is still a need for decentralized identification systems that do not rely on a centralized entity. We propose using Distributed Ledger Technology (DLT) to fulfill the needs. Although DLT and Distributed Hash Table (DHT) can be used as technologies in Decentralized Identifiers (DIDs), immutability and the growth of transactions are still challenging. This paper investigates DIDs under the W3C standard and DLT-based technology as one of the solutions for verifiable data registries in DIDs. We evaluate our proposed solution by comparing three models wrt. query time for verifiable data registries. Our proposed architecture for data registry achieves better query time by concealing old transactions from the main DLT.
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| 10. |
- Alizadeh, Morteza, 1987-, et al.
(author)
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DHT- and Blockchain-based Smart Identification for Video Conferencing
- 2022
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In: Blockchain: Research and Applications. - : Elsevier. - 2096-7209. ; 3:2
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Journal article (peer-reviewed)abstract
- Video conferencing applications help people communicate via the Internet and provide a significant and consistent basis for virtual meetings. However, integrity, security, identification, and authentication problems are still universal. Current video conference technologies typically rely on cloud systems to provide a stable and secure basis for executing tasks and processes. At the same time, video conferencing applications are being migrated from centralized to decentralized solutions for better performance without the need for third-party interactions. This article demonstrates a decentralized smart identification scheme for video conferencing applications based on biometric technology, machine learning, and a decentralized hash table combined with blockchain technology. We store users' information on a distributed hash table and transactional events on the distributed ledger after identifying users by implementing machine learning functions. Furthermore, we leverage distributed ledger technology's immutability and traceability properties and distributed hash table unlimited storage feature to improve the system's storage capacity and immutability by evaluating three possible architectures. The experimental results show that an architecture based on blockchain and distributed hash table has better efficiency but needs a longer time to execute than the two other architectures using a centralized database.
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