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Journal articles on the topic 'Merkle Trees'
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1
Kachko, O., and D. Televnyi. "The Kupyna hash function cryptanalysis with Merkle Trees Signature schemes." Radiotekhnika, no. 195 (December 28, 2018): 27–31. http://dx.doi.org/10.30837/rt.2018.4.195.03.
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The paper is devoted to the security analysis of the Kupyna (DSTU 7564:2014) hash function applied to Merkle tree signature schemes. The paper lists possible attacks on the hash, and their application for signature schemes. The results show expediency of using the Kypuna hash in Merkel schemes based on the performance, security levels and strength against known cryptanalytic attacks
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Wang, Xinyue, Weifan Lin, Weiting Zhang, Yiwen Huang, Zeyu Li, Qian Liu, Xinze Yang, Yifan Yao, and Chunli Lv. "Integrating Merkle Trees with Transformer Networks for Secure Financial Computation." Applied Sciences 14, no. 4 (February 8, 2024): 1386. http://dx.doi.org/10.3390/app14041386.
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In this paper, the Merkle-Transformer model is introduced as an innovative approach designed for financial data processing, which combines the data integrity verification mechanism of Merkle trees with the data processing capabilities of the Transformer model. A series of experiments on key tasks, such as financial behavior detection and stock price prediction, were conducted to validate the effectiveness of the model. The results demonstrate that the Merkle-Transformer significantly outperforms existing deep learning models (such as RoBERTa and BERT) across performance metrics, including precision, recall, accuracy, and F1 score. In particular, in the task of stock price prediction, the performance is notable, with nearly all evaluation metrics scoring above 0.9. Moreover, the performance of the model across various hardware platforms, as well as the security performance of the proposed method, were investigated. The Merkle-Transformer exhibits exceptional performance and robust data security even in resource-constrained environments across diverse hardware configurations. This research offers a new perspective, underscoring the importance of considering data security in financial data processing and confirming the superiority of integrating data verification mechanisms in deep learning models for handling financial data. The core contribution of this work is the first proposition and empirical demonstration of a financial data analysis model that fuses data integrity verification with efficient data processing, providing a novel solution for the fintech domain. It is believed that the widespread adoption and application of the Merkle-Transformer model will greatly advance innovation in the financial industry and lay a solid foundation for future research on secure financial data processing.
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He, Zichen. "Authenticating Account Balances in the Bitcoin Ecosystem via Merkle Trees." Highlights in Science, Engineering and Technology 85 (March 13, 2024): 494–500. http://dx.doi.org/10.54097/99pz5e96.
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Bitcoin, as the trailblazing cryptocurrency, has profoundly impacted global markets and stands as a formidable contender to traditional financial paradigms. Yet, even within the sophisticated framework of Bitcoin, there remains potential for enhancement. Within the Bitcoin ecosystem, lightweight nodes operate without storing all transaction details. Instead, they retain only the block headers' content and specific transactional data pertinent to their own operations. To authenticate a transaction's presence in the blockchain, these lightweight nodes seek a Merkle proof from the full nodes. However, a challenge arises when lightweight nodes aim to validate the accuracy of their account balances sourced from full nodes. The latter relies on a data structure known as the Unspent Transaction Outputs (UTXO) for streamlined balance computation. In contrast, lightweight nodes grapple with ascertaining the veracity of such balance calculations. A viable solution lies in leveraging the available space in every block's coinbase transaction, which permits arbitrary modifications. By arranging the UTXO within a Merkle tree structure and embedding its root into the coinbase transaction's available space, account balance verification for lightweight nodes can be significantly enhanced using the Merkle proof. While such modifications to the Bitcoin protocol might trigger soft forks, the risk of hard forks remains absent.
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Kachko, O. G., and D. Televnyi. "THE KUPYNA HASH FUNCTION CRYPTANALYSIS WITH THE MERKLE TREES SIGNATURE SCHEMES." Telecommunications and Radio Engineering 78, no. 8 (2019): 683–89. http://dx.doi.org/10.1615/telecomradeng.v78.i8.40.
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Martínez, Víctor Gayoso, Luis Hernández-Álvarez, and Luis Hernández Encinas. "Analysis of the Cryptographic Tools for Blockchain and Bitcoin." Mathematics 8, no. 1 (January 15, 2020): 131. http://dx.doi.org/10.3390/math8010131.
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Blockchain is one of the most interesting emerging technologies nowadays, with applications ranging from cryptocurrencies to smart contracts. This paper presents a review of the cryptographic tools necessary to understand the fundamentals of this technology and the foundations of its security. Among other elements, hash functions, digital signatures, elliptic curves, and Merkle trees are reviewed in the scope of their usage as building blocks of this technology.
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Zajac, Pavol. "Ephemeral Keys Authenticated with Merkle Trees and Their Use in IoT Applications." Sensors 21, no. 6 (March 13, 2021): 2036. http://dx.doi.org/10.3390/s21062036.
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Public key algorithms based on quasi-cyclic binary moderate-density parity-check codes (QC-MDPCs) and QC low-density parity-check codes (QC-LDPCs) codes for key encapsulation and encryption submitted to the NIST post-quantum competition (Bit Flipping Key Encapsulation (BIKE), QC-MDPC KEM, LEDA) are vulnerable against reaction attacks based on decoding failures. To protect algorithms, authors propose to limit the key usage, in the extreme (BIKE) to only use ephemeral public keys. In some authenticated protocols, we need to combine each key with a signature, which can lead to increased traffic overhead, especially given the large signature sizes of some of the proposed post-quantum signature schemes. We propose to combine ephemeral public keys with a simple Merkle tree to obtain a server authenticated key encapsulation/transport suitable for TLS-like handshake protocols. This allows a very simple public key verification on the client, leading to efficient protocols suitable for Internet of Things applications.
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Zou, Yu, Kazi Abu Zubair, Mazen Alwadi, Rakin Muhammad Shadab, Sanjay Gandham, Amro Awad, and Mingjie Lin. "ARES: Persistently Secure Non-Volatile Memory with Processor-transparent and Hardware-friendly Integrity Verification and Metadata Recovery." ACM Transactions on Embedded Computing Systems 21, no. 1 (January 31, 2022): 1–32. http://dx.doi.org/10.1145/3492735.
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Emerging byte-addressable Non-Volatile Memory (NVM) technology, although promising superior memory density and ultra-low energy consumption, poses unique challenges to achieving persistent data privacy and computing security, both of which are critically important to the embedded and IoT applications. Specifically, to successfully restore NVMs to their working states after unexpected system crashes or power failure, maintaining and recovering all the necessary security-related metadata can severely increase memory traffic, degrade runtime performance, exacerbate write endurance problem, and demand costly hardware changes to off-the-shelf processors. In this article, we designed and implemented ARES, a new FPGA-assisted processor-transparent security mechanism that aims at efficiently and effectively achieving all three aspects of a security triad—confidentiality, integrity, and recoverability—in modern embedded computing. Given the growing prominence of CPU-FPGA heterogeneous computing architectures, ARES leverages FPGA’s hardware reconfigurability to offload performance-critical and security-related functions to the programmable hardware without microprocessors’ involvement. In particular, recognizing that the traditional Merkle tree caching scheme cannot fully exploit FPGA’s parallelism due to its sequential and recursive function calls, we (1) proposed a Merkle tree cache architecture that partitions a unified cache into multiple levels with parallel accesses and (2) further designed a novel Merkle tree scheme that flattened and reorganized the computation in the traditional Merkle tree verification and update processes to fully exploit the parallel cache ports and to fully pipeline time-consuming hashing operations. Beyond that, to accelerate the metadata recovery process, multiple parallel recovery units are instantiated to recover counter metadata and multiple Merkle sub-trees. Our hardware prototype of the ARES system on a Xilinx U200 platform shows that ARES achieved up to 1.4× lower latency and 2.6× higher throughput against the baseline implementation, while metadata recovery time was shortened by 1.8 times. When integrated with an embedded processor, neither hardware changes nor software changes are required. We also developed a theoretical framework to analytically model and explain experimental results.
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Iavich, Maksim, Tamari Kuchukhidze, and Razvan Bocu. "A Post-Quantum Digital Signature Using Verkle Trees and Lattices." Symmetry 15, no. 12 (December 6, 2023): 2165. http://dx.doi.org/10.3390/sym15122165.
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Research on quantum computers has advanced significantly in recent years. If humanity ever creates an effective quantum computer, many of the present public key cryptosystems can be compromised. These cryptosystems are currently found in many commercial products. We have devised solutions that seem to protect us from quantum attacks, but they are unsafe and inefficient for use in everyday life. In the paper, hash-based digital signature techniques are analyzed. A Merkle-tree-based digital signature is assessed. Using a Verkle tree and vector commitments, the paper explores novel ideas. The authors of this article present a unique technology for developing a post-quantum digital signature system using state-of-the-art Verkle tree technology. A Verkle tree, vector commitments, and vector commitments based on lattices for post-quantum features are used for this purpose. The concepts of post-quantum signature design utilizing a Verkle tree are also provided in the paper.
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Gang, Feng, and DaHuan Wei. "Dynamic Deduplication Algorithm for Cross-User Duplicate Data in Hybrid Cloud Storage." Security and Communication Networks 2022 (July 22, 2022): 1–9. http://dx.doi.org/10.1155/2022/8354903.
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The escalating growth of distributed big data in hybrid cloud storage architecture introduces a new set of challenges. Constantly, content enrichment puts pressure on capacity. Nonetheless, the explosion of user data places a significant strain on broadband and storage capacity. Consequently, many cloud storage providers will implement deduplication to compress data, reduce transfer bandwidth, and reduce cloud storage space. In cloud storage systems, it is a data compression and storage optimization method. By locating and removing redundant data, it can save storage space and bandwidth. An MTHDedup deduplication strategy based on the Merkle hash tree is presented in a hybrid cloud environment to address the issue of convergent encryption algorithms being susceptible to brute-force attacks and ciphertext computation time overhead. Merkle hash trees are constructed using additional encryption algorithms to generate encryption keys during file- and block-level deduplication, ensuring that generated ciphertexts are unpredictable. The method is effective against both internal and external brute-force attacks, thereby increasing data security. Our method reduces the computational burden of ciphertext generation and the key storage space, and the performance advantage increases with the number of privilege sets.
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Ferrer, Eduardo Castelló, Thomas Hardjono, Alex Pentland, and Marco Dorigo. "Secure and secret cooperation in robot swarms." Science Robotics 6, no. 56 (July 28, 2021): eabf1538. http://dx.doi.org/10.1126/scirobotics.abf1538.
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The importance of swarm robotics systems in both academic research and real-world applications is steadily increasing. However, to reach widespread adoption, new models that ensure the secure cooperation of large groups of robots need to be developed. This work introduces a method to encapsulate cooperative robotic missions in an authenticated data structure known as a Merkle tree. With this method, operators can provide the “blueprint” of the swarm’s mission without disclosing its raw data. In other words, data verification can be separated from data itself. We propose a system where robots in a swarm, to cooperate toward mission completion, have to “prove” their integrity to their peers by exchanging cryptographic proofs. We show the implications of this approach for two different swarm robotics missions: foraging and maze formation. In both missions, swarm robots were able to cooperate and carry out sequential tasks without having explicit knowledge about the mission’s high-level objectives. The results presented in this work demonstrate the feasibility of using Merkle trees as a cooperation mechanism for swarm robotics systems in both simulation and real-robot experiments, which has implications for future decentralized robotics applications where security plays a crucial role.
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Sun, Nigang, Yuanyi Zhang, and Yining Liu. "A Privacy-Preserving KYC-Compliant Identity Scheme for Accounts on All Public Blockchains." Sustainability 14, no. 21 (November 6, 2022): 14584. http://dx.doi.org/10.3390/su142114584.
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Cryptocurrencies have the potential to enable socioeconomic growth throughout the world by offering easier access to capital and financial services. However, many virtual asset service providers (VASPs) that offer cryptocurrency services lack identity management and can be accessed anonymously, which has led to their services being exploited by criminal activities such as money laundering and illegal foreign exchange. Such crimes have a negative impact on socioeconomic sustainability. Building identity systems on blockchains can help VASPs improve their identity management to combat cryptocurrency-based crimes so VASPs can better serve the social economy and achieve their sustainability goals. However, existing solutions have privacy problems because the identity provider can associate users’ identities with their wallet accounts. In addition, there is currently no solution that can support all public blockchains unconditionally, as current solutions can only support EVM-compliant blockchains or require additional work to support new blockchains. This article proposes a KYC (know your customer)-compliant identity scheme based on Ethereum using Merkle trees and smart contracts. The identity and wallet accounts are linked by the user rather than the KYC provider so, in general, no one but the user knows the association between the wallet accounts and the identity, which protects privacy. For suspicious accounts, supervisors can trace their identities and thus achieve supervision. In addition, the scheme supports identifying accounts on all public blockchains by using Merkle trees and smart contracts to bind accounts on multiple blockchains to one identity and no extra work is required. Moreover, the scheme supports users to prove that their attributes meet the requirements of VASPs by adopting the BBS+ signature and the Sigma protocol.
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Alviano, Mario. "Hashcash Tree, a Data Structure to Mitigate Denial-of-Service Attacks." Algorithms 16, no. 10 (September 30, 2023): 462. http://dx.doi.org/10.3390/a16100462.
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Client puzzle protocols are widely adopted mechanisms for defending against resource exhaustion denial-of-service (DoS) attacks. Among the simplest puzzles used by such protocols, there are cryptographic challenges requiring the finding of hash values with some required properties. However, by the way hash functions are designed, predicting the difficulty of finding hash values with non-trivial properties is impossible. This is the main limitation of simple proof-of-work (PoW) algorithms, such as hashcash. We propose a new data structure combining hashcash and Merkle trees, also known as hash trees. In the proposed data structure, called hashcash tree, all hash values are required to start with a given number of zeros (as for hashcash), and hash values of internal nodes are obtained by hashing the hash values of child nodes (as for hash trees). The client is forced to compute all hash values, but only those in the path from a leaf to the root are required by the server to verify the proof of work. The proposed client puzzle is implemented and evaluated empirically to show that the difficulty of puzzles can be accurately controlled.
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M.Harshath, S.LingaPrabu, E.Prabhakar, R.Mohanraj, and R.Vignesh. "Blockchain Voting with Tamper Verification using Telegram Bot." international journal of engineering technology and management sciences 7, no. 2 (2023): 459–68. http://dx.doi.org/10.46647/ijetms.2023.v07i02.053.
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Blockchain technology has the potential to revolutionize the voting process by providing a secure and transparent method for recording votes. This paper proposes a voting system that utilizes blockchain technology, along with the Django web framework and Django administration for user profile updates, login using Aadhar number. The system incorporates a unique login feature that utilizes an Aadhar number, and two-step authentication through email OTP and private key authentication. The use of Merkle trees and SHA ensures a proof of work that prevents double voting, while tamper verification is achieved through a Telegram bot. The proposed system provides a secure, transparent, and efficient method for conducting elections, which is essential for ensuring a fair and democratic society.
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Wei, Franklin, Stephen Tate, Mahalingam Ramkumar, and Somya Mohanty. "A Scalable Trustworthy Infrastructure for Collaborative Container Repositories." Distributed Ledger Technologies: Research and Practice 1, no. 1 (September 30, 2022): 1–29. http://dx.doi.org/10.1145/3554760.
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Within cloud computing containerization has become ubiquitous. As the availability of pre-built containers increases there is a need for methods capable of efficiently securing large repositories of software containers. We present a “Trustworthy Container Repository” (TCR) system which provides security assurances (confidentiality, integrity, and authenticity) regarding such a repository in a scalable manner. Trust within the TCR architecture is rooted in a low-complexity, tamper-resistant trusted module, which leverages index-ordered Merkle trees (IOMTs) to efficiently track a large number of container images and provide assurances of repository integrity to its users. The key contributions of the study are, identification of the required security model, a novel TCR data-structure, and verifiable algorithms to operate on it. Through experiment, we observe closely logarithmic time complexity of the proposed system up to a high container count ( N = 2 25 ≈ 10 7 ).
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Reddy, Siddhant, and Dharmender Singh Kushwaha. "Framework for privacy preserving credential issuance and verification system using soulbound token." ITM Web of Conferences 56 (2023): 06002. http://dx.doi.org/10.1051/itmconf/20235606002.
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This paper proposes a framework for privacy-preserving credential issuance and verification over the public blockchain. The credential used in this framework is a soulbound token (SBT), a non-transferrable non-fungible token (NFT) verifiable on the blockchain. Once the issuing organization issues the credential, this framework gives the holder complete control of the credential. This privacy-preserving property allows the holder to selectively disclose the credential attributes in the verification process. The framework proposed suggests a decentralized credential recovery mechanism if the credential holder loses their private key. This paper compares this framework’s efficiency with different schemes based on privacy-preserving, selective disclosure, and decentralized credential recovery. This paper also compares the overhead for credential issuance and verification with Merkle trees. This paper also discusses the real-world use cases where this framework can be applied.
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Koushik S. and Annapurna P. Patil. "An Approach to Ensure Secure Inter-Cloud Data and Application Migration Using End-to-End Encryption and Content Verification." International Journal of Ambient Computing and Intelligence 13, no. 1 (January 2022): 1–21. http://dx.doi.org/10.4018/ijaci.293148.
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Cloud Computing is one of the most popular platforms in recent times and has many services to offer. The resources are deployed on the Cloud and are made available to cloud users over high-speed internet connectivity. Many enterprises think of migrating the data or application hosted from one Cloud to another based on the requirements. Migration from one Cloud to another Cloud requires security as it is vital for any data. This article presents a novel secure framework called ‘InterCloudFramework,’ considering well-established criteria to migrate various services across clouds with minimal supervision and interruption. Security is the primary concern to migrate the data among inter-clouds. The study incorporates the Elliptical-Curve Diffie-Hellman algorithm to encrypt the data and Merkle Hash Trees to check the integrity of the data. In addition to security during migration, the framework reduces the migration time of data or applications.
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Singh, A. "Secure Auditing and Deduplicating Data in Cloud." International Journal for Research in Applied Science and Engineering Technology 11, no. 5 (May 31, 2023): 6530–34. http://dx.doi.org/10.22214/ijraset.2023.53343.
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Abstract: With the widespread adoption of cloud computing, ensuring the security and integrity of data stored in the cloud has become a critical concern. This paper presents a novel approach for achieving secure auditing and deduplication of data in cloud environments. The proposed method addresses the challenges of data integrity verification and duplicate elimination while preserving the privacy of the stored data. By leveraging cryptographic techniques, including homomorphic encryption and Merkle hash trees, the system enables efficient and privacy- preserving auditing of data integrity. Additionally, a deduplication mechanism is integrated to eliminate redundant copies of data, reducing storage costs and improving efficiency. The proposed solution provides end-to-end security guarantees, ensuring that data remains confidential, unaltered, and readily available for authorized users. Extensive experimental evaluations demonstrate the effectiveness and efficiency of the proposed approach, making it a promising solution for secure data management in cloud environments
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Groza, Bogdan, and Pal-Stefan Murvay. "Secure Broadcast with One-Time Signatures in Controller Area Networks." International Journal of Mobile Computing and Multimedia Communications 5, no. 3 (July 2013): 1–18. http://dx.doi.org/10.4018/jmcmc.2013070101.
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Broadcast authentication in Controller Area Networks (CAN) is subject to real time constraints that are hard to satisfy by expensive public key primitives. For this purpose the authors study here the use of one-time signatures which can be built on the most computationally efficient one-way functions. The authors use an enhancement of the classical Merkle signature as well as the more recently proposed HORS signature scheme. Notably, these two proposals offer different trade-offs, and they can be efficiently paired with time synchronization to reduce the overhead caused by the re-initialization of the public keys, which would otherwise require expensive authentication trees. The authors do outline clear bounds on the performance of such a solution and provide experimental results on development boards equipped with Freescale S12X, a commonly used automotive grade micro-controller. The authors also benefit from the acceleration offered by the XGATE co-processor available on S12X derivatives which significantly increases the computational performances.
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Gueron, Shay, Edoardo Persichetti, and Paolo Santini. "Designing a Practical Code-Based Signature Scheme from Zero-Knowledge Proofs with Trusted Setup." Cryptography 6, no. 1 (January 27, 2022): 5. http://dx.doi.org/10.3390/cryptography6010005.
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This paper defines a new practical construction for a code-based signature scheme. We introduce a new protocol that is designed to follow the recent paradigm known as “Sigma protocol with helper”, and prove that the protocol’s security reduces directly to the Syndrome Decoding Problem. The protocol is then converted to a full-fledged signature scheme via a sequence of generic steps that include: removing the role of the helper; incorporating a variety of protocol optimizations (using e.g., Merkle trees); applying the Fiat–Shamir transformation. The resulting signature scheme is EUF-CMA secure in the QROM, with the following advantages: (a) Security relies on only minimal assumptions and is backed by a long-studied NP-complete problem; (b) the trusted setup structure allows for obtaining an arbitrarily small soundness error. This minimizes the required number of repetitions, thus alleviating a major bottleneck associated with Fiat–Shamir schemes. We outline an initial performance estimation to confirm that our scheme is competitive with respect to existing solutions of similar type.
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Gañán, Carlos, Jose L. Muñoz, Oscar Esparza, Jonathan Loo, Jorge Mata-Díaz, and Juanjo Alins. "BECSI: Bandwidth Efficient Certificate Status Information Distribution Mechanism for VANETs." Mobile Information Systems 9, no. 4 (2013): 347–70. http://dx.doi.org/10.1155/2013/139246.
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Certificate revocation is a challenging task, especiallyin mobile network environments such as vehicular ad Hoc networks (VANETs).According to the IEEE 1609.2 security standard for VANETs, public keyinfrastructure (PKI) will provide this functionality by means of certificate revocation lists (CRLs).When a certificate authority (CA)needs to revoke a certificate, itglobally distributes CRLs.Transmitting these lists pose a problem as they require high update frequencies and a lot of bandwidth. In this article, we propose BECSI, aBandwidth Efficient Certificate Status Informationmechanism to efficiently distributecertificate status information (CSI) in VANETs.By means of Merkle hash trees (MHT), BECSI allowsto retrieve authenticated CSI not onlyfrom the infrastructure but also from vehicles actingas mobile repositories.Since these MHTs are significantly smaller than the CRLs, BECSIreduces the load on the CSI repositories and improves the response time for the vehicles.Additionally, BECSI improves the freshness of the CSIby combining the use of delta-CRLs with MHTs.Thus, vehicles that have cached the most current CRLcan download delta-CRLs to have a complete list of revoked certificates.Once a vehicle has the whole list of revoked certificates, it can act as mobile repository.
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Chenchen Han, Chenchen Han, Gwang-Jun Kim Chenchen Han, Osama Alfarraj Gwang-Jun Kim, Amr Tolba Osama Alfarraj, and Yongjun Ren Amr Tolba. "ZT-BDS: A Secure Blockchain-based Zero-trust Data Storage Scheme in 6G Edge IoT." 網際網路技術學刊 23, no. 2 (March 2022): 289–95. http://dx.doi.org/10.53106/160792642022032302009.
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<p>With the rapid development of 6G communication technology, data security of the Internet of Things (IoT) has become a key challenge. This paper first analyzes the security issues and risks of IoT data storage in 6G, and then constructs a blockchain-based zero-trust data storage scheme (ZT-BDS) in 6G edge IoT to ensure data security. Under this framework, an improved scratch-off puzzle based on Proof of Recoverability (PoR) is firstly constructed to realize distributed IoT data storage, which can reduce resource consumption compared with other existing schemes. Secondly, the accumulator is used to replace the Merkle trees to store IoT data in the blockchain. Since the accumulator can provide not only membership proof, but also non-membership proof, the proposed blockchain-based data storage scheme is more secure. Thirdly, PoW is replaced by an improved PoR scheme as the consensus protocol. On the one hand, PoR can verify the integrity of data, which will further enhance the security of IoT data; on the other hand, the proposed PoR is composed of polynomial commitment, which can reduce bandwidth with the aid of the aggregation function of polynomial commitment. Experimental comparisons show that our scheme has better bandwidth and storage capacity.</p> <p> </p>
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Varveris, Dimitrios, Athanasios Styliadis, Panteleimon Xofis, and Levente Dimen. "Tree Architecture & Blockchain Integration: An off-the-shelf Experimental Approach." WSEAS TRANSACTIONS ON ENVIRONMENT AND DEVELOPMENT 19 (October 10, 2023): 969–77. http://dx.doi.org/10.37394/232015.2023.19.91.
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Temporally sensitive tree modeling and urban park spatially explicit simulation offer advantages to large-scale landscape planning and design, especially in the context of smart applications for virtual parks and forests, while Blockchain technology provides collaborative engineering, data integrity, and information confidence. A proof-of-concept 2.5D tree architecture and Blockchain integration technique (distributed Internet-of-Trees images, “IoTr-images”) was presented as a low-cost metaverse case study that affects the forest monitoring and digital landscape architecture design infrastructures. At the core of the proposed feature-based parametric modeling methodology is a 2.5D tree CAD model composed of two perpendicular 2D tree frames on which recorded tree texture has been assigned. A “Batch command-line programming” technique has been implemented, as a user-defined routine at the top of a commercial CAD platform, to describe the proposed off-the-self method and to create tangible tree-image NFT tokens (Internet-of-Trees-images Blockchain). As important findings were recorded, the add-in planning intelligence, the superior data integrity, and confidence, the offline relaxed error-free CAD design, and the superiority in terms of time and cost compared to traditional 3D tree modeling methods (laser scanning, close-range photogrammetry, etc.); as well as the satisfactory tree modeling accuracy for smart forest monitoring and landscape architecture applications. The proposed 2.5D parametric tree model added new value to the CAD-Blockchain integration industry because a plain “Blockchain/Merkle hash tree” tracks tree geometry growth and texture change temporarily with simple parametric transactions (i.e. controlled hash tree magnification/scaling). So, metaverse functionality (decentralized, autonomous, coordinated, and parallel design; same-data sharing; data validation), modification and redesign ability, and planning intelligence are effectively supported by the proposed technique. Main contributions are regarded as the ability for smart forest distributed surveillance and collaborative parallel landscape architecture design, open-source Web-based educational simulations, as well as the potential for off-the-shelf contractual collaborative frameworks (smart contracts between designers and clients). Stratification based on forest types improved above-ground biomass (AGB) estimation, especially when AGB was greater than 500 Mg/ha, using the proposed “IoTr-images” technique. So, this research provides new insight into AGB modeling and monitoring. Finally, the proposed method’s robustness has been validated by performance evaluation testing.
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M. Dillibabu, M. Dillibabu, S. Kumari S. Kumari, T. Saranya T. Saranya, and R. Preethi R. Preethi. "Assured Protection & Veracity for Cloud Data Using Merkle Hash Tree Algorithm." Indian Journal of Applied Research 3, no. 3 (October 1, 2011): 124–26. http://dx.doi.org/10.15373/2249555x/mar2013/39.
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Francis, Andrew R., and Mike Steel. "Which Phylogenetic Networks are Merely Trees with Additional Arcs?" Systematic Biology 64, no. 5 (June 11, 2015): 768–77. http://dx.doi.org/10.1093/sysbio/syv037.
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Исаков, Igor Isakov, Манцева, and Marina Mantseva. "Determining the size and viability of pollen of local and introduced species of birch trees." Forestry Engineering Journal 5, no. 3 (November 15, 2015): 33–40. http://dx.doi.org/10.12737/14151.
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We, with the help of an optical microscope, measurements were taken of length and width of pollen grains and their viability determined by the method of staining solution iodine – chloral hydrate. Studied species such as downy birch (B. pubescens Ehrh), the Karelian birch (B. pendu-la Roth var. Carelica Merkl.) dalecarlica and birch (Betula dalecarlica L). All the necessary work of collecting material was produced in the spring of 2015 on the territory of Semiluksky nursery in the Voronezh region. The research data were obtained about the size and viability of pollen types is presented and conclusions are made.
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Ouyang, Kelsey, David X. Zheng, and George W. Agak. "T-Cell Mediated Immunity in Merkel Cell Carcinoma." Cancers 14, no. 24 (December 9, 2022): 6058. http://dx.doi.org/10.3390/cancers14246058.
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Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4+, CD8+, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.
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Li, Yanmin, Zhengping Wang, Ting Guo, Shenghua Liu, and Chenchen Feng. "Treatment-related adverse events and response rate to immune checkpoint inhibition." Journal of International Medical Research 48, no. 3 (November 28, 2019): 030006051988645. http://dx.doi.org/10.1177/0300060519886454.
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Background Immune checkpoint inhibition (ICI) represents a novel treatment modality for refractory cancers, and improving prediction of potential responders is critical. Method We hypothesized that ICI is a systemic-effecting mechanism. The objective response rate (ORR) for anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination therapy was plotted against the corresponding all-grade and grade 3–4 (G3/4) treatment-related adverse events (TRAEs) across several cancer types using an extensive literature search (MEDLINE and Google Scholar; December 1, 2012–December 30, 2017). Results Sixty-six eligible studies comprised 76 cohorts and 25 cancer types. A significant correlation was present between all-grade or G3/4 TRAEs and the ORR. The correlation coefficient was 0.5 for all-grade and 0.4 for G3/4 TRAEs, suggesting that >50% of the differences in the ORR across cancer types may be reflected by TRAEs and 40% of ORR differences may be predicted by G3/4 TRAEs. Hodgkin’s lymphoma and Merkel cell carcinoma showed a better response, while adrenocortical cancer, breast cancer, and uveal melanoma showed a worse response, compared with that predicted by TRAE. Conclusion There is a strong relationship between TRAEs and ICI activity across multiple cancers. The toxicity profile compared with the ORR to ICIs should be investigated in phase I trials.
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Hashida, Yumiko, Masayuki Imajoh, Mikio Kamioka, Ayuko Taniguchi, Naoto Kuroda, Kazuhiko Hayashi, Hideki Nakajima, Shigetoshi Sano, and Masanori Daibata. "Phylogenetic analysis of Merkel cell polyomavirus based on full-length LT and VP1 gene sequences derived from neoplastic tumours in Japanese patients." Journal of General Virology 95, no. 1 (January 1, 2014): 135–41. http://dx.doi.org/10.1099/vir.0.058149-0.
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Most Merkel cell polyomavirus (MCPyV) gene sequences have been reported from Western countries and few data are available for the virus sequences from other geographical areas, especially Asia. Thus, we performed phylogenetic analyses based on the nucleotide sequences of the full-length large T-antigen (LT) and viral protein 1 (VP1) genes derived from a variety of cancers in Japanese patients and compared them with sequences from Caucasians. The LT and VP1 gene-based phylogenetic trees identified two main genetic clades. One clade comprised strains isolated from Caucasians, whereas all of the Japanese tumour-derived MCPyV strains belonged to another clade. These findings confirm that most of the MCPyV strains present in Japan form a clade, distinct from Caucasian strains.
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Jaiswar, Namrata, Soham Deodhar, Harish Gupta, and Prof Dnyaneshwar Kapse. "E -Voting System using Blockchain." International Journal for Research in Applied Science and Engineering Technology 11, no. 4 (April 30, 2023): 2090–95. http://dx.doi.org/10.22214/ijraset.2023.50618.
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Abstract: Designing a voting system that ensures fairness, privacy, and security is a significant challenge. The lack of trust in election systems among large sections of society worldwide is a major concern for democracy. Flawed voting systems pose a threat to democracies, including governing bodies, co-operating societies, and student councils. Vote rigging, hacking of electronic voting machines (EVMs), election manipulation, and booth capturing are the key issues with the current electoral system. To address these issues, we propose using novel technologies such as blockchain and Merkel trees, which are wellknown for their security benefits. Our system builds on popular blockchain frameworks that provide blockchain as a service, while preserving participants' anonymity and enabling public scrutiny. Blockchain is a unique technology of our time that promises to enhance the resilience of digital voting platforms. It presents an opportunity to leverage the benefits of blockchain, such as cryptographic foundations and transparency, to achieve an efficient digital voting system.
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Yang, Ruxia, Hongchao Gao, Fangyuan Si, and Jun Wang. "Advancing User Privacy in Virtual Power Plants: A Novel Zero-Knowledge Proof-Based Distributed Attribute Encryption Approach." Electronics 13, no. 7 (March 29, 2024): 1283. http://dx.doi.org/10.3390/electronics13071283.
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In virtual power plants, diverse business scenarios involving user data, such as queries, transactions, and sharing, pose significant privacy risks. Traditional attribute-based encryption (ABE) methods, while supporting fine-grained access, fall short of fully protecting user privacy as they require attribute input, leading to potential data leaks. Addressing these limitations, our research introduces a novel privacy protection scheme using zero-knowledge proof and distributed attribute-based encryption (DABE). This method innovatively employs Merkel trees for aggregating user attributes and constructing commitments for zero-knowledge proof verification, ensuring that user attributes and access policies remain confidential. Our solution not only enhances privacy but also fortifies security against man-in-the-middle and replay attacks, offering attribute indistinguishability and tamper resistance. A comparative performance analysis demonstrates that our approach outperforms existing methods in efficiency, reducing time, cost, and space requirements. These advancements mark a significant step forward in ensuring robust user privacy and data security in virtual power plants.
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Ведерников (Vedernikov), Дмитрий (Dmitrij) Николаевич (Nikolaevich), and Игорь (Igor') Александрович (Aleksandrovich) Казарцев (Kazartsev). "VARIATIONS OF THE CHEMICAL COMPOSITION OF EXTRACTIVE KIDNEYS OF THE KIDNEYS BERES OF ST. PETERSBURG AND THE LENINGRAD REGION." chemistry of plant raw material, no. 2 (January 9, 2018): 123–30. http://dx.doi.org/10.14258/jcprm.2018022743.
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The article is devoted to the differences in the composition of extractive substances of vegetative buds of birch trees in St. Petersburg and the Leningrad region and its change. Buds of birch (Betulae gemmae) are a medicinal product and are included in the state register of medicines. The substances soluble in acetone were studied by chromatography-mass spectrometry method after preliminary methylation with diazomethane. The retention indices of the identified compounds are given. Earlier, the structure of compounds was established by methods of NMR spectroscopy.Birch buds from the surveyed areas contain sesquiterpenoids and flavonoids. These components correspond to the classical notions of the composition of the buds. However, specimens of birch trees were found containing only triterpenoids and fatty acids in the buds, and also a combination of all the listed compounds - the intermediate composition. This tendency was observed in the Betula pendula Roth. birch, Betula pubescens Ehrh., Betula pendula var. carelica Merckl., Betula krylovii G.V.Krylov in the arboretum of the St. Petersburg Forestry University and observed on the Betula pendula and, Betula pubescens in St. Petersburg and the Leningrad region. Presumably one type of chemical composition can be replaced by another in time. The change in the composition was recorded for several years on specimens of birches.Various reasons for this phenomenon are discussed.
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Bespalov, Yuri, Alberto Garoffolo, Lyudmila Kovalchuk, Hanna Nelasa, and Roman Oliynykov. "Probability Models of Distributed Proof Generation for zk-SNARK-Based Blockchains." Mathematics 9, no. 23 (November 24, 2021): 3016. http://dx.doi.org/10.3390/math9233016.
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The paper is devoted to the investigation of the distributed proof generation process, which makes use of recursive zk-SNARKs. Such distributed proof generation, where recursive zk-SNARK-proofs are organized in perfect Mercle trees, was for the first time proposed in Latus consensus protocol for zk-SNARKs-based sidechains. We consider two models of a such proof generation process: the simplified one, where all proofs are independent (like one level of tree), and its natural generation, where proofs are organized in partially ordered set (poset), according to tree structure. Using discrete Markov chains for modeling of corresponding proof generation process, we obtained the recurrent formulas for the expectation and variance of the number of steps needed to generate a certain number of independent proofs by a given number of provers. We asymptotically represent the expectation as a function of the one variable n/m, where n is the number of provers m is the number of proofs (leaves of tree). Using results obtained, we give numerical recommendation about the number of transactions, which should be included in the current block, idepending on the network parameters, such as time slot duration, number of provers, time needed for proof generation, etc.
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Sakhvon, Vital V. "NESTING FEATURES OF BLACKBIRD (TURDUS MERULA) IN URBAN GREEN SPACES IN MINSK." Journal of the Belarusian State University. Ecology., no. 4 (December 25, 2021): 46–53. http://dx.doi.org/10.46646/2521-683x/2021-4-46-53.
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Synurbic populations of birds are characterized by specific features that differ from those of wild populations of the same species, which is the result of adaptation to living in cities. The paper analyses some parameters of breeding of the Blackbird (Turdus merula) in two park in Minsk and compares them with the breeding biology of wild Blackbirds in natural habitats. During the years 2015-2017 and 2019-2021, 74 nests of urban Blackbird were obtained. For comparison, data on 245 nest of this species in natural landscapes were used.As a result, it was found that the nest selection in urban Blackbirds remains similar to wild Blackbirds in forests, and the differences are explained by the peculiarities of forestry activities carried out in urban parks. More than 74 % of all nests were built in the undergrowth layer, while most of the nests were located on the Norway spruce (59.72 %). A majority of urban Blackbirds started laying first eggs relatively later (from 21.04 to 10.05) than forest birds (from 11.04 to 30.04), which most likely results from the adaptation of birds to a significant recreational load from humans during the period when the trees have not come into leaf yet. Nevertheless, no differences were found in the average clutch size between urban (4.17 ± 0.72 eggs) and forest (4.51 ± 0.64 eggs) birds. The low breeding success of the Blackbird (39.4 %) in the urbanized area testifies to the fact that the homeostasis of the relatively high number of the urban Blackbird population in Minsk is most likely maintained due to the constant influx of individuals from local suburban forests.
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Lu, You, Qiming Fu, Xuefeng Xi, and Zhenping Chen. "Cloud data acquisition and processing model based on blockchain." Journal of Intelligent & Fuzzy Systems 39, no. 4 (October 21, 2020): 5027–36. http://dx.doi.org/10.3233/jifs-179988.
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Data outsourcing has gradually become a mainstream solution, but once data is outsourced, data owners will without the control of the data hardware, there is a possibility that the integrity of the data will be destroyed objectively. Many current studies have achieved low network overhead cloud data set verification by designing algorithmic structures (e.g., hashing, Merkel verification trees); however, cloud service providers may not recognize the incompleteness of cloud data to avoid liability or business factors fact. There is a need to build a secure, reliable, non-tamperable, and non-forgeable verification system for accountability. Blockchain is a chain-like data structure constructed by using data signatures, timestamps, hash functions, and proof-of-work mechanisms. Using blockchain technology to build an integrity verification system can achieve fault accountability. Blockchain is a chain-like data structure constructed by using data signatures, timestamps, hash functions, and proof-of-work mechanisms. Using blockchain technology to build an integrity verification system can achieve fault accountability. This paper uses the Hadoop framework to implement data collection and storage of the HBase system based on big data architecture. In summary, based on the research of blockchain cloud data collection and storage technology, based on the existing big data storage middleware, a large flow, high concurrency and high availability data collection and processing system has been realized.
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Verschraegen, Claire F., Guy Jerusalem, Edward F. McClay, Nicholas Iannotti, Charles H. Redfern, Jaafar Bennouna, Franklin L. Chen, et al. "Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study." Journal for ImmunoTherapy of Cancer 8, no. 2 (September 2020): e001064. http://dx.doi.org/10.1136/jitc-2020-001064.
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IntroductionAvelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).MethodsIn a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.ResultsOverall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred.ConclusionAvelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study.Trial registration detailsClinicalTrials.gov NCT01772004; registered January 21, 2013.
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Kelly, Karen, Jeffrey R. Infante, Matthew H. Taylor, Manish R. Patel, Michael S. Gordon, Deborah Jean Lee Wong, Nicholas Iannotti, et al. "Safety profile of avelumab in patients with advanced solid tumors: A JAVELIN pooled analysis of phase 1 and 2 data." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 3059. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.3059.
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3059 Background: Avelumab is a fully human IgG1 anti–PD-L1 antibody with clinical activity in several tumor types. Pooled safety data from a large phase 1 trial in various tumors and a phase 2 trial in Merkel cell carcinoma (NCT01772004, NCT02155647) were analyzed to further characterize the safety profile of avelumab. Methods: Patients (pts) received avelumab 10 mg/kg 1-hour IV Q2W until progression, unacceptable toxicity, or withdrawal. Treatment-related adverse events (TRAEs) were graded by NCI CTCAE. In post hoc analyses, immune-related adverse events (irAEs) were identified via an expanded AE list and medical review, and infusion-related reaction (IRR) events were identified based on prespecified MedDRA terms, occurring within 1 day or related symptoms that resolved within 2 days of infusion. Results: In 1,738 pts analyzed (phase 1, n = 1,650; phase 2, n = 88) who received ≥1 dose of avelumab for a median of 12 weeks (range 2-138), the most common any grade TRAEs were fatigue (n = 307, 18%), IRR (n = 295, 17%), and nausea (n = 150, 9%). 177 pts (10%) had a grade ≥3 TRAE; most common were fatigue and elevated lipase (17 [1%] each). TRAEs led to discontinuation in 107 pts (6%). Four pts (0.2%) died due to a TRAE. Any grade irAEs occurred in 247 pts (14%), which were grade ≥3 in 39 pts (2%) and considered serious in 43 pts (2%). The most common any grade irAEs were thyroid disorder (n = 98, 6%) and rash (n = 90, 5%). Other irAEs (eg, colitis, hepatitis, pneumonitis, adrenal insufficiency, myositis) each occurred in < 2%. irAEs led to discontinuation in 34 pts (2%). IRR or related symptoms (eg, chills, pyrexia, hypersensitivity) occurred in 439 pts (25%), which were grade 3 in 9 pts (0.5%) and grade 4 in 3 pts (0.2%). An IRR occurred at first infusion in 79% and within first 4 doses in 99%; 63/439 pts (14%) had IRR recurrence in later cycles. IRR led to dose interruption in 152 (9%), infusion rate reduction in 124 (7%), and discontinuation in 35 pts (2%). Conclusions: This large pooled analysis confirms that avelumab has an acceptable safety profile. A minority of pts experienced a grade ≥3 TRAE or irAE and discontinuation due to TRAEs was uncommon. IRRs mostly occurred at first infusion and the rate of recurrence was low. Clinical trial information: NCT01772004, NCT02155647.
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Dowlatshahi, Mitra, Victor Huang, Ahmed E. Gehad, Ying Jiang, Adam Calarese, Jessica E. Teague, Andrew A. Dorosario, et al. "Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T-Cell Exhaustion in Reducing T-Cell Responses." Journal of Investigative Dermatology 133, no. 7 (July 2013): 1879–89. http://dx.doi.org/10.1038/jid.2013.75.
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Tarelkina, Tatiana V., Ludmila L. Novitskaya, Natalia A. Galibina, Yulia L. Moshchenskaya, Kseniya M. Nikerova, Nadezhda N. Nikolaeva, Irina N. Sofronova, Diana S. Ivanova, and Ludmila I. Semenova. "Expression Analysis of Key Auxin Biosynthesis, Transport, and Metabolism Genes of Betula pendula with Special Emphasis on Figured Wood Formation in Karelian Birch." Plants 9, no. 11 (October 22, 2020): 1406. http://dx.doi.org/10.3390/plants9111406.
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Auxin status in woody plants is believed to be a critical factor for the quantity and quality of the wood formed. It has been previously demonstrated that figured wood formation in Karelian birch (Betula pendula Roth var. carelica (Merckl.) Hämet-Ahti) is associated with a reduced auxin level and elevated sugar content in the differentiating xylem, but the molecular mechanisms of the abnormal xylogenesis remained largely unclear. We have identified genes involved in auxin biosynthesis (Yucca), polar auxin transport (PIN) and the conjugation of auxin with amino acids (GH3) and UDP-glucose (UGT84B1) in the B. pendula genome, and analysed their expression in trunk tissues of trees differing in wood structure. Almost all the investigated genes were overexpressed in Karelian birch trunks. Although Yucca genes were overexpressed, trunk tissues in areas developing figured grain had traits of an auxin-deficient phenotype. Overexpression of GH3s and UGT84B1 appears to have a greater effect on figured wood formation. Analysis of promoters of the differentially expressed genes revealed a large number of binding sites with various transcription factors associated with auxin and sugar signalling. These data agree with the hypothesis that anomalous figured wood formation in Karelian birch may be associated with the sugar induction of auxin conjugation.
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Takács, Attila, Csaba Szabóky, Balázs Tóth, Miklós Bozsó, János Kutas, Szilárd Molnár, Gábor Farkas, et al. "Bionomics and host plants of the invasive Cydia interscindana (Möschler, 1866) (Lepidoptera, Tortricidae), an emerging pest in the Carpathian Lowlands." Nota Lepidopterologica 45 (January 14, 2022): 53–64. http://dx.doi.org/10.3897/nl.45.74236.
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Cydia interscindana (Möschler, 1866) has spread through several European countries in the past few years, becoming an invasive pest of ornamental trees. It was collected in Hungary for the first time in a pheromone trap set for Cydia pomonella (Linnaeus, 1758) in 2014. Here we discuss its recent distribution in Hungary based on intensive sampling between 2018 and 2020, which showed the dispersal of the pest by humans. Two formerly unknown host plants are also recorded. The damage caused by the larvae, the external morphology of the adult male, larva, pupa (described for the first time) and pupal exuviae are presented. We also analyse DNA barcodes, identifying this pest for the first time via DNA sequencing of immature stages. Introduction Cydia interscindana is native in the Mediterranean region, where it was described by Möschler in 1866 from Andalusia. It is distributed in Mediterranean countries including Portugal (Corley 2004), Spain (Férriz et al. 2006), France (Lévêque et al. 2017) and Italy (Minelli 1995). Later the species was recorded in the British Isles (Knill-Jones 2020), Belgium (De Prins 2016), Switzerland (Swisslepteam 2010), Slovakia (Pastorális et al. 2018) and Russia (Caucasus; Schurov et al. 2017). In Hungary, Cydia interscindana adults were caught by a sticky delta pheromone trap (CSALOMON RAG type) for Cydia pomonella (Linnaeus 1758) in 2014 during a study on swarming dynamics of the latter pest in Budapest. This provided the first record of the species in the Carpathian basin (Szabóky 2014; Takács and Szabóky 2015). In the Mediterranean region larvae feed on Juniperus oxycedrus (L.) (Miller 1990). In Belgium the larva was recorded on Juniperus spp. (Meert et al. 2019). J. oxycedrus is not native in Hungary, but Cupressus × leylandii A.B. Jacks. & Dallim 1926, Platycladus orientalis (L.) Franco 1949 and Chamaecyparis lawsoniana (A. Murray bis) Parl. 1864 are popular evergreens used as ornamental trees both in parks and gardens. In Hungary several pests of these plants have been recorded, all probably introduced with imported plants; in the literature, 11 Lepidoptera, nine Coleoptera and six Hemiptera species have been mentioned already (Csóka and Kovács 1999; Maráczi 2013; Bozsik et al. 2016; Schurov et al. 2017). However, until the end of the 2000s, only Scolytidae (Coleoptera) species caused serious damage (Bozsik and Szőcs 2017). In 2012, an outbreak of the formerly detected (Muskovits 2001) Lamprodila festiva (Linnaeus 1767) (Buprestidae) took place in Budapest (Németh 2012) causing serious damage on Platycladus orientalis and several ornamental gymnosperm species. This outbreak was certainly caused by introduced specimens, that had arrived with trees from the Mediterranean region where this beetle is a well-known pest (Merkl 2016), whose abundance in Hungary increases due to climatic change (Csóka et al. 2018). Based on the available data, in Hungary this beetle pest has also been blamed for all the damage caused on Cupressus, Platycladus and Chamaecyparis trees and management has been carried out only against them. In 2018, a larva of L. festiva, an unidentified caterpillar and a freshly emerged specimen of Cydia interscindana were collected simultaneously from a Leyland cypress in Székesfehérvár (Central Hungary). In that year, similar Lepidoptera larvae were found in three neighbouring villages: Velence, Sukoró and Pákozd. To identify the sampled caterpillar, DNA analysis was undertaken. Additionally, in 2019–2020 a country-wide investigation was carried out to map the distribution and abundance of C. interscindana and gather data on bionomics of this pest in the Carpathian basin.
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D'Angelo, Sandra P., Jeffrey Russell, Jessica Cecile Hassel, Celeste Lebbe, Bartosz Chmielowski, Guilherme Rabinowits, Patrick Terheyden, et al. "First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9530. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9530.
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9530 Background: MCC is a rare, aggressive skin cancer. Avelumab is a fully human anti–PD-L1 antibody. In a phase 2 study in pts with distant mMCC who progressed after prior chemotherapy (JAVELIN Merkel 200; NCT02155647), avelumab showed a manageable safety profile and durable responses, including an objective response rate (ORR) of 31.8%, estimated 6-month durable response rate of 29%, and 6-month overall survival rate of 69%. Here, we report preliminary results from a separate cohort of pts with chemotherapy-naïve mMCC enrolled in the same study. Methods: Eligible pts with mMCC and no prior systemic treatment for metastatic disease received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1). Adverse events (AEs) were assessed by NCI CTCAE v4.0. Results: As of Dec 30, 2016, 29/112 planned pts had been enrolled. Median age was 75.0 years (range 47–87). Median treatment duration was 8.1 weeks (range 2.0–37.9). Of 16 pts with ≥3 months of follow-up, unconfirmed ORR was 68.8% (95% CI 41.3–89.0) with CR in 18.8%; confirmed ORR was 56.3% (95% CI 29.9–80.2; 1 unconfirmed PR with discontinuation). Of 25 pts with ≥6 weeks of follow-up, unconfirmed ORR was 64.0% (95% CI 42.5–82.0). All responses were ongoing at last follow-up, including in 5/5 pts with ≥6 months of follow-up (potential to confirm responses). 20/29 pts (69.0%) had a treatment-related AE (TRAE), including grade 3–4 TRAE in 5 pts (17.2%). TRAEs led to discontinuation in 5 pts (17.2%): 2 pts with infusion-related reaction, and 1 pt each with elevated AST and ALT, cholangitis, and paraneoplastic syndrome. There were no treatment-related deaths. 21/29 pts (72.4%) remain on treatment. Conclusions: In initial results from a cohort of chemotherapy-naïve pts with mMCC, avelumab was associated with early responses and a manageable safety profile, consistent with findings for second-line or later avelumab treatment in a previous cohort. These results suggest that responses mature to become durable and the use of 1L avelumab may increase the probability of response vs later-line treatment. Enrollment and follow-up in this 1L cohort are ongoing. Clinical trial information: NCT02155647.
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Bhatia, Shailender, Suzanne Louise Topalian, William Howard Sharfman, Tim Meyer, Christopher D. Lao, Lorena Fariñas-Madrid, Lot A. Devriese, et al. "Non-comparative, open-label, international, multicenter phase I/II study of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic merkel cell carcinoma (MCC) (CheckMate 358)." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 9506. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.9506.
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9506 Background: MCC is a rare and aggressive skin cancer. Programmed death-ligand 1 (PD-L1) is often upregulated in MCC and blockade of PD-L1 or its receptor, PD-1, has improved survival for patients with metastatic MCC. Anti–PD-1 combined with anti–CTLA-4 has been reported to improve outcomes over anti–PD-1 monotherapy (NCT03071406; Kim S et al., Lancet 2022), however further investigation is needed. CheckMate 358 (NCT02488759) assessed NIVO ± IPI in 2 non-randomized MCC cohorts. Methods: Eligible pts had recurrent or metastatic MCC, ≤ 2 prior therapies, ECOG performance status (PS) 0–1, and no prior immune checkpoint inhibitor (ICI) therapy. Pts were eligible regardless of PD-(L)1 status. Pts received NIVO 240 mg Q2W or NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W for ≤ 24 months (m) or until disease progression, unacceptable toxicity, or consent withdrawal. Imaging was conducted Q8W in year 1 and Q12W thereafter. Planned sample sizes were 23 pts for NIVO and 40 pts for NIVO + IPI. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included duration of response (DOR), investigator-assessed progression-free survival (PFS), and overall survival (OS). Results: 68 pts received NIVO (n = 25) or NIVO + IPI (n = 43) with ≥ 24 m follow-up (median: NIVO, 62.5 m; NIVO + IPI, 24.4 m). In the NIVO arm, median age was 66 yrs (range, 27–88), 10 (40.0%) pts had ECOG PS of 1, and 15 (60.0%) were treatment-naive. In the NIVO + IPI arm, median age was 70 yrs (range, 48–85), 27 (62.8%) pts had ECOG PS of 1, and 33 (76.7%) were treatment-naive. Treatment duration was 15.8 m in the NIVO arm, and 7.9 m for NIVO and 6.0 m for IPI in the NIVO + IPI arm. Efficacy and safety outcomes are summarized in the table. ORR was 60.0% (95% CI, 38.7–78.9) in the NIVO arm and 58.1% (95% CI, 42.1–73.0) in the NIVO + IPI arm. The most common reasons for treatment discontinuation were disease progression (NIVO, 28.0%; NIVO + IPI, 32.6%) or study-drug toxicity (NIVO, 20.0%; NIVO + IPI, 25.6%). There was 1 study drug-related death in each arm (NIVO, pneumonitis; NIVO + IPI, gastrointestinal motility disorder). Conclusions: Both NIVO and NIVO + IPI show durable clinical efficacy in advanced MCC. While the non-randomized trial design limits comparisons between the arms, results do not suggest additional efficacy benefit with IPI added to NIVO. Higher incidence of grade 3/4 TRAEs observed in the combination arm could have resulted in shorter treatment duration. Clinical trial information: NCT02488759 . [Table: see text]
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Davar, Diwakar, John George Knecht, Andrae Lavon Vandross, Cesar Augusto Perez, David Michael Miller, John D. Powderly, Alberto Bessudo, et al. "Phase 1/2 study of XTX101, a masked, tumor-selective Fc-modified anti-CTLA4, in patients with advanced solid tumors." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e14685-e14685. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e14685.
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e14685 Background: XTX101 is a tumor-selective, anti-CTLA-4 monoclonal antibody (mAb) engineered with covalently linked peptides that mask CTLA-4 antigen-binding regions. The masking peptides are cleaved by matrix metalloproteases that are more active in the tumor microenvironment (TME) compared with healthy tissues. XTX101 is designed with 2 Fc domain mutations (S239D and I332E) which enhance binding to Fcγ receptors and are intended to improve effector function, resulting in depletion of regulatory T-cells in the TME. In a murine model, XTX101 at 0.3 mg/kg achieved similar tumor growth inhibition as 3 mg/kg of an ipilimumab analog, suggesting higher relative potency of XTX101 over ipilimumab (Powderly SITC 2021). Methods: Interim results of first-in-human, Phase 1 portion of study XTX101-01/02-001 (NCT04896697) are reported here. Part 1A examines XTX101 monotherapy in 3+3 dose escalation. Part 1B is evaluating pharmacodynamic (PD) biomarkers. Results: As of January 27, 2023, 22 patients (pts) with advanced solid tumors were enrolled including colorectal (n = 3), pancreatic (n = 3), non-small cell lung (n = 3), squamous cell skin (n = 2), breast (n = 2), uterine (n = 2), cervical, prostate, Fallopian tube cancer, leiomyosarcoma and Merkel cell carcinoma in Part 1A, and melanoma and colorectal cancer in Part 1B. Pts had a median of 3 prior lines of therapy (1-10). Dose levels (DL) of 7, 20 and 60 mg every 3 weeks (Q3W) were cleared (1 dose limiting toxicity (DLT) of colitis among 8 patients treated at 60 mg Q3W), while 2 DLTs of colitis were reported among 6 pts at 180 mg Q3W. An alternative dosing schedule of 150 mg every 6 weeks (Q6W) was implemented based on clinical and pharmacokinetic (PK) data, and no DLTs were reported among 5 pts at this alternative schedule. There were no grade (G) 4 or 5 treatment-related (TR) adverse events (AEs) on the study. G3 TRAEs included colitis (n = 4), infusion reaction (IR, n = 3) and lymphopenia (n = 2). There were no skin, endocrine or liver-related TRAEs of any grade. One patient with squamous cell lung cancer treated at 150 mg Q6W dose had an unconfirmed partial response and continues on treatment. PK exposure with 150 mg Q6W schedule were comparable to 2 cycles of 60 mg Q3W. Among 8 pts treated at 60 mg Q3W and 5 treated at 150 mg Q6W, 2 out of 13 patients (15%) experienced G3 colitis, 1 pt G2 colitis and 1 pt G2 diarrhea. All colitis AEs improved with immunosuppression and resolved. There were 2 IRs at 60 mg Q3W, while no IR occurred with the Q6W schedule. Based on the totality of clinical and PK data, 150 mg Q6W is the recommended Phase 2 dose (RP2D), and enrollment in part 1B is ongoing at this dose. Conclusions: XTX101 is a Fc-engineered, masked, tumor-activated, anti-CTLA-4 mAb in development for advanced solid tumors. At RP2D, the preliminary safety profile is differentiated from systemically active anti-CTLA4 mAb. Updated clinical data, PK, immunogenicity and PD data from the study will be presented. Clinical trial information: NCT04896697 .
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Vasselli, James Robert, Sophia Frentzas, Andrew James Weickhardt, Paul L. de Souza, Jenny Tang, Tim Wyant, Inbar Amit, Yanay Ofran, and Aron Knickerbocker. "Trial in progress: A phase 1-2, first-in-human, open label, dose escalation and expansion study of AU-007, a monoclonal antibody that binds to IL-2 and inhibits IL-2Rα binding, in patients with advanced solid tumors." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): TPS2671. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.tps2671.
Full textAbstract:
TPS2671 Background: AU-007 is a computationally designed, monoclonal antibody that binds to IL-2 on its CD25 binding epitope. AU-007 bound IL-2 (A/IL-2) cannot bind to high affinity trimeric IL-2 receptors (IL-2R) consisting of CD25, CD122, and CD132 expressed on Tregs and vascular endothelium, but its binding to low affinity dimeric IL-2Rs (CD122 and CD132) expressed on T effector and NK cells is unhindered. Thus, AU-007 redirects endogenously produced or exogenous IL-2 (aldesleukin) towards activation of immune stimulating T effector and NK cells, while diminishing Treg activation and expansion. AU-007 will also bind and redirect newly secreted endogenous IL-2 resulting from A/IL-2 driven T cell expansion in the tumor, converting a Treg mediated autoinhibitory loop into an immune stimulating loop. AU-007 is unique in the IL-2 therapeutic field as engineered exogenous, recombinant “non-CD25” IL-2s in development cannot address the autoinhibitory effect of endogenous IL-2. Preclinically, AU-007 has been demonstrated to capture endogenous human IL-2 in vivo. AU-007 with a single low dose of IL-2 has demonstrated efficacy in multiple cancer models and has an excellent safety profile in non-human primates. Methods: This first-in-human, multicenter, open label Phase 1- 2 study evaluates the safety, tolerability, and initial efficacy of AU-007 +/- aldesleukin in patients with advanced solid tumors (CT-2021-CTN-03938-1). Phase 1 consists of 3 escalation arms each starting with a single 1+2 escalation cohort followed by 3+3 escalation cohorts to define the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD). Patients with melanoma, renal cell carcinoma (RCC) and 17 selected solid tumors are eligible. Prior treatment with check point inhibitors is allowed. In Arm A, escalating doses of Q2w AU-007 are evaluated in sequential escalation cohorts. In Arm B, a single dose of aldesleukin is given with the initial AU-007 dose. AU-007 is given at a fixed dose Q2w with an escalating single aldesleukin dose in sequential escalation cohorts. In Arm C, AU-007 is evaluated in combination with aldesleukin, both given Q2w. AU-007 is administered at a fixed dose with an escalating dose of aldesleukin in sequential cohorts. The Phase 2 cohort expansion portion of the study evaluates the initial efficacy at the RP2D defined in escalation cohorts A, B, and C in 3 matching expansion cohorts of up to 20 patients each. Patients with advanced melanoma, RCC and other tumors including, but not limited to, Merkel Cell Carcinoma, NSCLC, and urothelial cancer are eligible. Enrolment to the study commences in Australia, with US sites planned to open later in 2022. Clinical trial information: CT-2021-CTN-03938-1.
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Zheng, Hong, Shin Mineishi, David F. Claxton, Junjia Zhu, Chenchen Zhao, Bei Jia, W. Christopher Ehmann, Seema Naik, Natthapol Songdej, and Raymond J. Hohl. "Effect of Avelumab to Immune Response in AML: A Phase I Study of Avelumab in Combination with Decitabine As First Line Treatment of Unfit Patients." Blood 134, Supplement_1 (November 13, 2019): 3939. http://dx.doi.org/10.1182/blood-2019-125153.
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Introduction: Treatment of AML remains challenging. Decitabine is a hypomethylating agent (HMA) commonly used for treating AML. However, its efficacy is limited. Recent success targeting immune checkpoints offers great promise and several agents blocking the PD-1 pathway have been FDA approved for cancer therapy. It has been demonstrated that HMA enhances PD-1 pathway in MDS and AML patients, providing a strong rationale for combining HMA and PD-1 inhibition in AML treatment. Avelumab is a PD-L1 antibody that blocks the interaction between PD-L1 and PD-1. It has been FDA approved for treating Merkel cell and urothelial carcinoma and in combination with axitinib for renal cell carcinoma. This phase I study aimed to investigate the safety of avelumab combining with decitabine in AML. In addition, extensive correlative studies were performed to define the effect of avelumab on the immune response. Methods: This is a single arm, open label phase I study to evaluate safety and tolerability of avelumab in combination with decitabine in patients with untreated AML, who are unfit for intensive chemotherapy. Decitabine was given at 20mg/m2 IV day 1-5, every 28 days. Avelumab was given at 10mg/kg IV day 1, every 14 days. Each treatment cycle was 28 days. Treatment length was up to one year or until progression. In the initial stage, classic "3+3" design was applied to determine safety. Patients were evaluated for DLTs in cycle 1. In the expansion stage, a cohort of 9 additional patients using the same regimen was planned. For correlative studies, blood and bone marrow samples were collected prior to and post initiation of avelumab. Flow cytometry-based assays for immune phenotype and functions were performed. Results: Seven patients have been treated on protocol. Median age was 71 (62-78). Most patients (6/7) carried adverse cytogenetics per ELN 2017 risk stratification. Median number of treatment cycles was 2 (range 1-12). No DLT was detected. The most frequent TEAEs (any grade or cause) were anorexia (86%), fatigue (71%), edema (71%), pleural effusion (71%), febrile neutropenia (57%) and respiratory failure (57%). Two treatment-related TRAEs were observed: fever (14%) and pneumonitis (14%). TRAEs led to treatment discontinuation in 1 patient (14%). The trial was closed before accrual met for the best interest of patients due to the recent FDA approval of venetoclax, a novel treatment for the same patient population. Among the 7 patients accrued, 1 patient achieved CR, 3 patients stable disease, 1 had progression of disease; response could not be assessed in 2 patients due to death before response assessment. To investigate the effect of avelumab on immune response, we conducted complex immune assays using blood samples collected from each patient prior to vs. 1 month post treatment. We observed no alteration in the frequency of each immune component (NK, NKT, B cells, DCs, Monocytes, CD4 T cells, CD8 T cells, and Treg) upon avelumab and decitabine treatment. However, there was an increase in effector memory differentiation while decreased terminal differentiated subsets in CD8 T cells. We next performed comprehensive phenotypic and functional analysis of CD8 T cells. Data of the first accrued 6 patients are shown here (Figure 1); the data from patient 7 is underway and will be integrated into the presentation at the meeting. We observed a strong trend of up-regulation of activation markers and co-stimulatory receptors (CD69, CD226, CD28, ICOS and 4-1BB) on CD8 T cells post treatment of avelumab and decitabine. In contrast, the expression of inhibitory molecules, including TIGIT, TIM-3, CD160, LAG-3, 2B4 and BTLA, were trending down. Consistently, CD8 T cell function was enhanced in majority of patients, manifested by higher expression of granzyme B, perforin and Ki67, as well as more cytokine release (IFN-γ and TNF-α) upon in vitro TCR engagement. Importantly, avelumab is likely the major contributor for the positive regulatory effect as studies on samples from patients who received decitabine alone did not show the same trend. Conclusion: In this phase I study, we demonstrated that avelumab in combination with decitabine as first line treatment of unfit patients with AML is safe and tolerable. CD8 T cell response trends up upon avelumab treatment. Our study strongly supports the addition of avelumab to AML treatment with a potential to improve anti-leukemia immunity. Disclosures Zheng: Pfizer: Research Funding. Claxton:Daiichi Sankyo Co. and Ambit Biosciences Corp, Astellas Pharma, Novartis Pharmaceuticals, Incyte Corporation, Cyclacel Pharmaceuticals, Inc, Celegene Corporation, Medimmune, Inc, Merck Sharp & Dohme Corp., Gilead Sciences, Inc.: Research Funding. Naik:Celgene: Other: Advisory board.
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Berinstein, Neil L., Isabelle Bence-Bruckler, Nicholas Allen Forward, Pierre Laneuville, Joy Mangel, Douglas A. Stewart, Irina Amitai, et al. "Clinical Effectiveness of Combination Immunotherapy DPX-Survivac, Low Dose Cyclophosphamide, and Pembrolizumab in Recurrent/Refractory DLBCL: The Spirel Study." Blood 136, Supplement 1 (November 5, 2020): 16. http://dx.doi.org/10.1182/blood-2020-136751.
Full textAbstract:
Background: Recurrent/refractory (r/r) DLBCL presents a major treatment challenge, especially in the setting of patients who are ineligible for, or relapsing after, potentially curative treatments such as autologous stem cell transplant (ASCT) and chimeric antigen receptor T cell (CAR-T) therapy. Efficacious treatment options that are well-tolerated and easily accessible in this population represent a critical unmet medical need. DPX-Survivac is a targeted T cell activation therapy against cancers expressing survivin. Survivin plays an essential role in cancer biology and represents a target of choice to disrupt tumour progression. DPX-Survivac's mechanism of action relies on its ability to generate robust and durable survivin-specific T cells that migrate to, infiltrate and kill tumour cells. DPX-Survivac is administered with intermittent, low dose cyclophosphamide (CPA) used as an immunomodulator. In nonclinical studies, treatment with DPX-Survivac increases PD-L1 and PD-1 expression providing the rationale for combination with pembrolizumab. Methods: "SPiReL" is a Phase 2 non-randomized, open label, efficacy and safety study. Subjects with r/r DLBCL with confirmed survivin expression are eligible for participation. Subjects must also be ineligible for potentially curative therapy. The treatment and testing regimen is shown in the figre below. The primary objective of SPiReL is to document a minimum Objective Response Rate (ORR) of 24% (in 6/25 subjects) using the modified Cheson criteria (2007). Secondary objectives include safety, duration of response and time to next treatment. Exploratory endpoints include T cell response, tumour immune cell infiltration, and biomarker analysis. Results: At data cut-off, 22 subjects have been enrolled in the study. The median age is 75.5 years (50-82). Thirteen of 22 subjects (59.1%) are GCB sub-type, 8 subjects (36.4%) are non-GCB and 1 subject (4.5%) has primary cutaneous DLBCL, leg type. The median number of prior therapies is 2 (1-7), with 4 subjects having previously undergone ASCT and 5 subjects with transformed disease. Of the 22 enrolled subjects, 8 are not evaluable per protocol for clinical efficacy due to early disease progression. Four subjects are active on treatment, 3 of which have not yet reached the first time point for assessment. Clinical outcome was analyzed for the Full Analysis Set (FAS) (n=19) and in the Per Protocol (PP) analysis (n=11). Of 11 subjects in the PP, 7 subjects (63.6%) have achieved an objective response, meeting the study's primary endpoint; 3 subjects (27.3%) with a CR and 4 subjects (36.4%) with a PR. Three subjects (27.3%) achieved SD and thus clinical benefit was demonstrated in 10/11 (90.9%) of evaluable subjects. Two subjects (18.2%) have completed the 1 year treatment period, 8 subjects (72.7%) discontinued treatment due to disease progression, and 1 subject (9.2%) discontinued treatment due to an unrelated Adverse Event (AE). Including the entire FAS, the objective response rate was 7/19 (36.8%). This treatment combination is well-tolerated, only 11% of Treatment Related AEs (TRAEs) were assessed as Grade 3 or higher. The majority of the Grade 1 and 2 TRAEs were Injection Site Reactions (ISRs) related to DPX-Survivac. Ten serious AEs were reported, of which 3 were considered related to study treatment. No subjects have discontinued study treatment due to a TRAE. Analyses of peripheral blood T cell responses to survivin by ELISpot assay shows that 7/7 subjects who achieved an objective response have survivin-specific T cell response. One subject with PD also showed a survivin-specific T cell response, supporting the mechanism of action and the role of DPX-Survivac in anti-tumor activity. Summary: DPX-Survivac and low dose CPA in combination with pembrolizumab, demonstrates promising clinical activity in recurrent/refractory DLBCL with 10/11 (90.9%) of evaluable subjects deriving clinical benefit with minimal toxicity. The primary endpoint of this study has been reached with 7/11 (63.6%) of evaluable subjects achieving an objective response warranting further exploration of DPX-Survivac in this population. Enrollment is continuing to further define the patient population most likely to benefit from this well-tolerated therapy. Figure 1 Disclosures Bence-Bruckler: Merck: Membership on an entity's Board of Directors or advisory committees. Forward:Seattle Genetics: Research Funding; IMV: Research Funding; Merck: Research Funding; Astellas: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; IMV: Membership on an entity's Board of Directors or advisory committees; Calgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Stewart:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Teva: Honoraria. Bramhecha:IMV Inc.: Current Employment. Conlon:IMV Inc.: Current Employment. OffLabel Disclosure: Keytruda (pembrolizumab). Indicated for use in melanoma, nonÃÆ'Ã'¢Ã¢ââ'¬Å¡Ã¢â€šâ'¬ÃƒÂ¢Ã¢â€šâ'¬Ã…“small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), classical Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL), urothelial carcinoma, microsatellite instability-high (MSI-H) or a mismatch repair deficient (dMMR) solid tumor, gastric or gastroesophageal junction (GEJ) adenocarcinoma, squamous cell carcinoma of the esophagus, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma (MCC), and renal cell carcinoma (RCC).
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Arnold, Manuel, Manuel C. Voelkle, and Andreas M. Brandmaier. "Score-Guided Structural Equation Model Trees." Frontiers in Psychology 11 (January 28, 2021). http://dx.doi.org/10.3389/fpsyg.2020.564403.
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Structural equation model (SEM) trees are data-driven tools for finding variables that predict group differences in SEM parameters. SEM trees build upon the decision tree paradigm by growing tree structures that divide a data set recursively into homogeneous subsets. In past research, SEM trees have been estimated predominantly with the R package semtree. The original algorithm in the semtree package selects split variables among covariates by calculating a likelihood ratio for each possible split of each covariate. Obtaining these likelihood ratios is computationally demanding. As a remedy, we propose to guide the construction of SEM trees by a family of score-based tests that have recently been popularized in psychometrics (Merkle and Zeileis, 2013; Merkle et al., 2014). These score-based tests monitor fluctuations in case-wise derivatives of the likelihood function to detect parameter differences between groups. Compared to the likelihood-ratio approach, score-based tests are computationally efficient because they do not require refitting the model for every possible split. In this paper, we introduce score-guided SEM trees, implement them in semtree, and evaluate their performance by means of a Monte Carlo simulation.
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Daemen, Joan, Bart Mennink, and Gilles Van Assche. "Sound Hashing Modes of Arbitrary Functions, Permutations, and Block Ciphers." IACR Transactions on Symmetric Cryptology, December 13, 2018, 197–228. http://dx.doi.org/10.46586/tosc.v2018.i4.197-228.
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Cryptographic hashing modes come in many flavors, including Merkle-Damgård with various types of strengthening, Merkle trees, and sponge functions. As underlying primitives, these functions use arbitrary functions, permutations, or block ciphers. In this work we provide three simple proofs, one per primitive type, that cover all modes where the input to the primitive consists of message bits, chaining value bits, and bits that only depend on the mode and message length. Our approach generalizes and simplifies over earlier attempts of Dodis et al. (FSE 2009) and Bertoni et al. (Int. J. Inf. Sec. 2014). We prove tight indifferentiability bounds for modes using each of these three primitive types provided that the mode satisfies some easy to verify conditions.
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Dr. Sonali Ridhorkar and Mr. Setu Sagar Mishra. "Implementing Quantum Resistant Algorithm in Blockchain-Based Applications." International Journal of Advanced Research in Science, Communication and Technology, April 30, 2024, 650–59. http://dx.doi.org/10.48175/ijarsct-17899.
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With quantum computing evolving very fast as we speak, the security and integrity of blockchain-based applications will become the most crucial aspect. A proposal is raised to use blockchain technology as a platform for writing and probating ‘wills’. Blockchain technology in drafting and probating wills makes them safe from manipulations, highly secure, and transparent. It also dramatically decreases the time required without catering for the challenges created by the current system. [9] This paper presents a new method for will transfer and inheritance management by implementing quantum-resistant algorithms in the security architecture of a blockchain decentralized application (DApp). The system uses IPFS Network for data storage and quantum-safe algorithms as retrieval and sending algorithms. The system includes Quantum-Resistant Dilithium Signatures and Merkle trees as the fundamental components for safeguarding the transfers of assets and claims for inheritance. Quantum-Resistant Dilithium Signatures offer an unbreakable shield against quantum attacks that are expected to happen, which in turn safeguards the privacy and authenticity of transactions. While Merkle trees are responsible for the organization of inheritance claims in an effective and tamper-proof manner, the introduced system incorporates smart contracts to address the execution of an inheritance case, adding more security and automation to the asset distribution process. The system ensures a robust security framework by integrating quantum-resistant algorithms at the very core of the blockchain DApp for instance, retrieval and sending. This research is of great significance to blockchain technology which is the emerging technology of the future because it addresses the existing threat of quantum computing by showing the feasibility of using quantum-resistant algorithms in practical applications. As established by the findings, besides Quantum-Resistant Dilithium Signatures and Merkle trees, the systems of asset transfers and inheritance management within blockchain networks are enhanced in terms of safety and reliability. Hence, paving the road to the creation of more secure and trustworthy digital asset management systems.
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Kuznetsov, Oleksandr, Alex Rusnak, Anton Yezhov, Kateryna Kuznetsova, Dzianis Kanonik, and Oleksandr Domin. "Merkle Trees in Blockchain: A Study of Collision Probability and Security Implications." Internet of Things, April 2024, 101193. http://dx.doi.org/10.1016/j.iot.2024.101193.
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Davies, Jack. "Enhanced scalability and privacy for blockchain data using Merklized transactions." Frontiers in Blockchain 6 (January 9, 2024). http://dx.doi.org/10.3389/fbloc.2023.1222614.
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Blockchain technology has evolved beyond the use case of electronic cash and is increasingly used to secure, store, and distribute data for many applications. Distributed ledgers such as Bitcoin have the ability to record data of any kind alongside the transfer of monetary value. This property can be used to provide a source of immutable, tamper-evident data for a wide variety applications spanning from the supply chain to distributed social media. However, this paradigm also presents new challenges regarding the scalability of data storage protocols, such that the data can be efficiently accessed by a large number of users, in addition to maintaining privacy for data stored on the blockchain. Here, we present a new mechanism for constructing blockchain transactions using Merkle trees comprised of transaction fields. Our construction allows for transaction data to be verified field-wise using Merkle proofs. We show how the technique can be implemented either at the system level or as a second layer protocol that does not require changes to the underlying blockchain. This technique allows users to efficiently verify blockchain data by separately checking targeted individual data items stored in transactions. Furthermore, we outline how our protocol can afford users improved privacy in a blockchain context by enabling network-wide data redaction. This feature of our design can be used by blockchain nodes to facilitate easier compliance with regulations such as GDPR and the right to be forgotten.