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Sharding blockchains are proposed to solve the scalability problem while maintaining security and decentralization. However, there are still many issues to be solved. First, the member selection and assignment process is not analyzed strictly, which might lead to an increase in the adversary proportion. Second, current intra-shard consensus algorithms are inefficient. Besides, cross-shard transaction processing costs expensive system overhead. Moreover, a formal security framework is lacked. In this paper, we propose a novel secure scalable hybrid consensus (SSHC). First, we propose a fair sharding selection scheme to select committee members, including mining processes and member lists confirmation by a reference committee. Second, a pipelined Byzantine fault tolerance for intra-shard consensus is designed, combining the pipelined technology with threshold signatures. Third, we propose a responsive sharding transaction batch processing mechanism to handle cross-shard transactions, which reduces the number of calls to Byzantine fault tolerance algorithms. Fourth, a secure committee reconfiguration method is designed to update shard members efficiently. Furthermore, we employ a formal security framework to design and analyze a sharding blockchain. For an adversary whose computational power fraction is less than 1/3, by reasonably setting a corruption parameter and other related parameters, SSHC is proved to achieve consistency and liveness.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) have been investigated for biomedical applications, including novel contrast agents, magnetic tracers for tumor imaging, targeted drug delivery vehicles, and magneto-mechanical actuators for hyperthermia and thrombolysis. Despite significant progress, recent clinical reports have raised concerns regarding USPION safety related to endothelial cell dysfunction; however, there is limited information on factors contributing to these clinical responses. The influence of USPION surface chemistry on nanoparticle interactions with proteins may impact endothelial cell function leading to adverse responses. Therefore, the goal of this study was to assess the effects of carboxyl-functionalized USPION (CU) or amine-functionalized USPION (AU) (approximately 30 nm diameter) on biological responses in human coronary artery endothelial cells. Increased protein adsorption was observed for AU compared with CU after exposure to serum proteins. Exposure to CU, but not AU, resulted in a concentration-dependent decrease in cell viability and perinuclear accumulation inside cytoplasmic vesicles. Internalization of CU was correlated with endothelial cell functional changes under non-cytotoxic conditions, as evidenced by a marked decreased expression of endothelial-specific adhesion proteins (eg, vascular endothelial-cadherin and platelet endothelial cell adhesion molecule-1) and increased endothelial permeability. Evaluation of downstream signaling indicated endothelial permeability is associated with actin cytoskeleton remodeling, possibly elicited by intracellular events involving reactive oxygen species, calcium ions, and the nanoparticle cellular uptake pathway. This study demonstrated that USPION surface chemistry significantly impacts protein adsorption and endothelial cell uptake, viability, and barrier function. This information will advance the current toxicological profile of USPION and improve development, safety assessment, and clinical outcomes of USPION-enabled medical products.

Cloud storage is an effective way for data owners to outsource their data by remotely storing them in the cloud and enjoy on-demand high quality services. In traditional cloud storage systems, cloud data integrity verification relies on centralized entities and data is stored in a small number of storage servicers. However, these centralized entities and storage servicers may be untrustworthy, and malicious servicers may even refuse to perform a user’s query or update request. Though a few blockchain-based themes have been proposed to address some of these problems, they do not achieve decentralization, accountability, flexibility and practicability simultaneously. In this paper, we present Themis, an accountable P2P cloud storage scheme with smart contracts on Ethereum. Our scheme has the following advantages: First, cloud data integrity verification is decentralized and implemented by miners on blockchain without any trusted third party. Second, by carefully setting up the reward and punishment mechanism within a smart storage contract, all rational nodes will participate in the storage service following an accountable rule. Third, based on reliable information published on the blockchain, users are free to choose appropriate storage servicers who want to share idle storage, making storage service decentralized and flexible. Fourth, compared with the existing related systems, by adopting a payment at maturity method, the malicious behavior of breaking the contract after the servicer obtains some revenue is prevented, and the availability of user data within the specified period is enhanced. Fourthermore, we implement a prototype of Themis on Rinkeby, an Ethereum test network. Extensive experimental results demonstrate that our scheme is able to support a PB-level data storage in a single P2P storage service at a low cost and is feasible for practical deployment. And the entire decentralized arbitration process takes only 40 to 110 seconds.

Ethereum accelerates the transaction process through a quicker block creation design. Since the time interval between the generation of blocks is very short (about 15s), block propagation time in an inefficient network is not negligible compared with the block time interval. This lead to the production of a large number of orphan blocks. In order to solve the security problems that may be caused by the orphan block and improve the transaction processing efficiency, Ethereum introduces the uncle block mechanism, i.e., an orphan block may get part of minted reward if it gets a reference by a regular block. In this paper, we show the weakness of the uncle block mechanism. Firstly, we describe the specific differences of Ethereum selfish and stubborn mining in every state from the ones in Bitcoin. Secondly, we simulate possible attacks, and the results show that the Ethereum selfish and stubborn mining strategies not only increase the reward of an attacker but also decrease the security threshold. The security threshold refers to the proportion of the attacker's computational power that needs to be achieved in order to obtain a higher reward than he should. In a practical network congestion rate, the security threshold are weakened to 0.129 and 0.216 against the Lead stubborn mining strategy and the original selfish mining strategy, respectively. When the congestion rate is rising, the reward is increasing and the threshold is decreasing. Thirdly, possible strategies are evaluated to find out the optimal one in different settings. Fourthly, we also extend the evaluation by combining three eclipse attack strategies with selfish or stubborn mining. Most of combinations bring more advantages to an attacker than a single strategy.

Sensor nodes in wireless body-area networks are expected to use compressed sensing (CS) for ultralow-power consumption. For signal recovery in CS systems, compared with the software implementation, the hardware processor has superiority on power, real-time ability, and so on. Although orthogonal matching pursuit (OMP) is conventionally selected in hardware implementations, its low recovery performance is still a problem. We propose to use the subspace pursuit (SP) algorithm that can achieve higher recovery performance with less iteration to implement the hardware processor. First, a new SP by a square-root-free method and a computation reuse scheme are proposed to reduce the SP’s complexity. Then, the fully paralleled architectures and elaborate pipelines are proposed to improve the processing throughput. Finally, we give an FPGA implementation prototype. Simulations compared with OMP show that the traditional SP can improve more than 8 dB on recovery performance or it can reduce more than 31% sampling paths in sensor nodes. These benefits are kept by our proposed SP because our improvement does not modify the algorithmic nature. Nevertheless, the significant complexity reduction is achieved by our proposal. The proposed SP processor can recover ECG signals with 28.2 dB and achieve the processing throughput of 44.4 K vectors/s.

Endogenous partial denitrification (EPD) and denitrifying phosphorous removal (DPR) were combined in a novel A

In this paper, we study the existing blockchain consensus mechanisms that can be applied to access control scenarios and analyze advantages and disadvantages for each category. Besides, we divide access control procedures into policy formulation, storage, and request processing. For each procedure, we summarize existing methods and analyze possible problems. Finally, we give the potential future research directions. This paper provides a clear framework for access control, on which researchers can explore new types of blockchain-based access control solutions to solve the existing security and performance problems.

Studies of anticancer therapies in traditional cell culture models can demonstrate efficacy of direct-acting compounds but lack the 3-dimensional arrangement of the tumor cells and their tissue-specific microenvironments, both of which are important modulators of treatment effects in vivo. Bone cells reside in complex environments that regulate their fate and function. A bioengineered human bone-tumor model has been shown to provide a microphysiological niche for studies of cancer cell behavior. Here, we demonstrate successful transfer between 2 laboratories and utility of this model in efficacy studies using well-established chemotherapeutic agents. The bioengineered human bone-tumor model consisted of Ewing sarcoma (RD-ES) cancer cell aggregates infused into tissue-engineered bone that was grown from human mesenchymal stem cell-derived differentiated into osteoblasts within mineralized bone scaffolds. The tumor model was maintained in culture for over 5 weeks and subjected to clinically relevant doses of linsitinib, doxorubicin, cisplatin, methotrexate, vincristine, dexamethasone, or MAP (methotrexate, doxorubicin, and cisplatin combination). Drug administration cycles were designed to mimic clinical treatment regimens. The bioengineered tumors were evaluated days to weeks after the cessation of treatment to monitor the potential for relapse, using bioengineered bone and ES cell monolayers as controls. Drug binding to the scaffolds and media proteins and gene expression were also evaluated. We show that a bioengineered human bone tumor can be used as a microphysiological model for preclinical studies of anticancer drugs. We found that anticancer efficacy was achieved at concentrations approximating the human Cmax, in contrast to traditional ES cell monolayers. These studies show that the bone-tumor model can be successfully transferred between laboratories and has predictive power in preclinical studies. The effects of drugs on the bone tumors and healthy bone were studied in parallel, in support of the utility of this model for identification of new therapeutic targets.

Most present reconfiguration methods in sharding blockchains rely on a secure randomness, whose generation might be complicated. Besides, a reference committee is usually in charge of the reconfiguration, making the process not decentralized. To address the above issues, this paper proposes a secure and decentralized shard reconfiguration protocol, which allows each shard to complete the selection and confirmation of its own shard members in turn. The PoW mining puzzle is calculated using the public key hash value in the member list confirmed by the last shard. Through the mining and shard member list commitment process, each shard can update its members safely and efficiently once in a while. Furthermore, it is proved that our protocol satisfies the safety, consistency, liveness, and decentralization properties. The honest member proportion in each confirmed shard member list is guaranteed to exceed a certain safety threshold, and all honest nodes have an identical view on the list. The reconfiguration is ensured to make progress, and each node has the same right to participate in the process. Our secure and decentralized shard reconfiguration protocol could be applied to all committee-based sharding blockchains.

Summary Smart contracts are regarded as one of the most promising and appealing notions in blockchain technology. Their self-enforcing and event-driven features make some online activities possible without a trusted third party. Nevertheless, problems such as miscellaneous attacks, privacy leakage, and low processing rates prevent them from being widely applied. Various schemes and tools have been proposed to facilitate the construction and execution of secure smart contracts. However, a comprehensive survey for these proposals is absent, hindering new researchers and developers from a quick start. This paper surveys the literature and online resources on smart contract construction and execution over the period 2008–2020. We divide the studies into three categories: (1) design paradigms that give examples and patterns on contract construction, (2) design tools that facilitate the development of secure smart contracts, and (3) extensions and alternatives that improve the privacy or efficiency of the system. We start by grouping the relevant construction schemes into the first two categories. We then review the execution mechanisms in the last category and further divide the state-of-the-art solutions into three classes: private contracts with extra tools, off-chain channels, and extensions on core functionalities. Finally, we summarize several challenges and identify future research directions toward developing secure, privacy-preserving, and efficient smart contracts., The bigger picture Smart contracts are one of the most promising and appealing notions in blockchain technology. We provide a comprehensive review of state-of-the-art smart contract construction and execution schemes. We classify three major categories: (1) design paradigms that give examples and patterns on contract construction, (2) design tools that facilitate the development of secure smart contracts, and (3) extensions and alternatives that improve privacy or efficiency. We found that frequently occurred vulnerabilities, incomplete paradigms, inefficient analysis tools, low processing rate, limited contract complexity, and the lack of privacy are the main challenges that hinder the adoption of smart contracts. We identify several future research directions, including fair off-chain networks, practical implementations, scalable and automatic analysis tools, and private contracts with practical compilers., We conducted a comprehensive survey on the smart contract execution and construction schemes over 2008–2020. This work is aimed to provide insights for new researchers and developers in this field. According to our survey, problems such as privacy leakage, execution efficiency, and contract complexity have restricted the application scenarios of smart contracts. After categorizing the relevant schemes, we identify several future research directions, including fair off-chain schemes, practical implementations, scalable and automatic analysis tools, and private contracts with practical compilers.

Sharding is the prevalent approach to breaking the trilemma of simultaneously achieving decentralization, security, and scalability in traditional blockchain systems, which are implemented as replicated state machines relying on atomic broadcast for consensus on an immutable chain of valid transactions. Sharding is to be understood broadly as techniques for dynamically partitioning nodes in a blockchain system into subsets (shards) that perform storage, communication, and computation tasks without fine-grained synchronization with each other. Despite much recent research on sharding blockchains, much remains to be explored in the design space of these systems. Towards that aim, we conduct a systematic analysis of existing sharding blockchain systems and derive a conceptual decomposition of their architecture into functional components and the underlying assumptions about system models and attackers they are built on. The functional components identified are node selection, epoch randomness, node assignment, intra-shard consensus, cross-shard transaction processing, shard reconfiguration, and motivation mechanism. We describe interfaces, functionality, and properties of each component and show how they compose into a sharding blockchain system. For each component, we systematically review existing approaches, identify potential and open problems, and propose future research directions. We focus on potential security attacks and performance problems, including system throughput and latency concerns such as confirmation delays. We believe our modular architectural decomposition and in-depth analysis of each component, based on a comprehensive literature study, provides a systematic basis for conceptualizing state-of-the-art sharding blockchain systems, proving or improving security and performance properties of components, and developing new sharding blockchain system designs.

Angiogenesis is a complex process that is required for development and tissue regeneration and it may be affected by many pathological conditions. Chemicals and drugs can impact formation and maintenance of the vascular networks; these effects may be both desirable (e.g., anti-cancer drugs) or unwanted (e.g., side effects of drugs). A number of in vivo and in vitro models exist for studies of angiogenesis and endothelial cell function, including organ-on-a-chip microphysiological systems. An arrayed organ-on-a-chip platform on a 96-well plate footprint that incorporates perfused microvessels, with and without tumors, was recently developed and it was shown that survival of the surrounding tissue was dependent on delivery of nutrients through the vessels. Here we describe a technology transfer of this complex microphysiological model between laboratories and demonstrate that reproducibility and robustness of these tissue chip-enabled experiments depend primarily on the source of the endothelial cells. The model was highly reproducible between laboratories and was used to demonstrate the advantages of the perfusable vascular networks for drug safety evaluation. As a proof-of-concept, we tested Fluorouracil (1-1,000 μM), Vincristine (1-1,000 nM), and Sorafenib (0.1-100 μM), in the perfusable and non-perfusable micro-organs, and in a colon cancer-containing micro-tumor model. Tissue chip experiments were compared to the traditional monolayer cultures of endothelial or tumor cells. These studies showed that human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs. The data from the 3D models confirmed advantages of the physiological environment as compared to 2D cell cultures. We demonstrated how these models can be translated into practice by verifying that the endothelial cell source and passage are critical elements for establishing a perfusable model.

Effect of influent COD/NO

With the development of blockchain technology, the use of cryptocurrencies in online payments has become increasingly prevalent. Litecoin, proposed in 2011, is currently the fifth-largest cryptocurrency in market value. Due to certain characteristics, such as the use of pseudonyms as transaction addresses, user privacy could be protected to some extent. However, there are some problems about its privacy guarantees.In this paper, we aim to reveal the severity of deanonymization attacks on online Litecoin payments. Firstly, we simulate purchases on merchant websites accepting Litecoin and monitor trackers embedding on information and payment pages. Secondly, we conduct transaction-linkage attacks on simulated digital and physical transaction flows, respectively. Our results show that a tracker is more likely to find the target transaction on Litecoin blockchain by collecting the digital transaction flows and implementing transaction-linkage attacks. The number of digital transaction flows with anonymous set size 1 and 2 account for 95% and 5% of all digital transaction flows, respectively. The success rate of the transaction-linkage attack is 0.975. To get the optimal uncertainty parameters of transaction-linkage attacks, we introduce a refined deanonymization attack by making real purchases. Finally, we present two new privacy protection measures against transaction-linkage attacks.

Sharding blockchains could improve the transaction throughput and achieve scalibility, making the application fields of the blockchain technology more extensive. Cross-shard transactions account for a large fraction of transactions in a sharding blockchain, so the processing method of cross-shard transactions is of vital importance to the system efficiency. In this paper, we focus on the study of cross-shard transaction processing methods. Firstly, a summary of cross-shard transaction processing methods for sharding blockchains is given. Secondly, we propose RSTBP, which is built on the basis of a two phase commit protocol. In RSTBP, an input shard runs an intra-shard consensus algorithm, i.e., a Byzantine fault tolerance (BFT) algorithm, to process multiple inputs of different transactions simultaneously. For each input, a corresponding proof of availability is generated and sent to the relevant shards. Compared with previous schemes, the number of BFT calls is reduced by hundreds of times when processing the same number of transactions. Thirdly, RSTSBP is designed by making some modifications to RSTBP. The proofs of availability are constructed according to different shards. The Merkel tree structure is different from that of RSTBP to cut down message complexity of the proofs. Both of the two schemes are proved to satisfy the consistency, liveness and responsiveness properties, and improve the cross-shard transaction processing efficiency.

Sharding blockchains are promising in improving transaction throughput and achieving network scalability. Intra-shard consensus and cross-shard communication are two essential parts for almost every kind of sharding blockchain. However, some security problems still exist in current sharding solutions such as replay attacks, and there is still room for improvement in efficiency.

Bone defects are a significant cause of morbidity in the fields of orthopedics, maxillofacial surgery, and oral implantology, yet their treatment currently faces many challenges including the defect size and location, underlying disease, and microbial infection. Bacteria may be introduced to healing bone through several routes including colonization during open-wound trauma, introduction during surgery, from blood-borne bacteria, or infection of a medical device such as a bone screw. Unfortunately, current treatment strategies are often inadequate and lead to severe and costly consequences. To tackle the problem of infection during bone healing, novel biomaterials such as scaffolds, cements, surface-modified implants, and particles have been developed that comprise both antimicrobial and osteoconductive properties. The antimicrobial properties of these biomaterials typically stem from the addition of antimicrobial agents like antibiotics and silver nanoparticles to the composite material, while osteoconductive properties are conveyed by biomolecules such as growth factors or hydroxyapatite. By controlling modes of delivery and/or release kinetics, these antibacterial and osteoconductive therapeutic constructs are potentially capable of significantly improving bone healing. Recent findings have shown very promising results in the application of these constructs with dual functions in treating infected bone defects. Here, we summarize the advances within the last decade in particle technologies, implant coatings, tissue engineering, and bone cements with both antimicrobial and osteoconductive activity with an emphasis on fabrication and the performance of constructs in various in vitro and in vivo models.

The effect of nanoparticle surface coating characteristics on colloidal stability in solution is a critical parameter in understanding the potential applications of nanoparticles, especially in biomedicine. Here we explored the modification of the surface of poly(ethylene glycol)-coated superparamagnetic iron oxide nanoparticles (PEG-SPIOs) with the synthetic pseudotannin polygallol via interpolymer complexation (IPC). Changes in particle size and zeta potential were indirectly assessed via differences between PEG-SPIOs and IPC-SPIOs in particle velocity and scattering intensity using near-field light scattering. The local scattering intensity is correlated with the distance between the particle and waveguide, which is affected by the size of the particle (coating thickness) as well as the interactions between the particle and waveguide (related to the zeta potential of the coating). Therefore, we report here the use of near-field light scattering using nanophotonic force microscopy (using a NanoTweezerTM instrument, Halo Labs) to determine the changes that occurred in hydrated particle characteristics, which is accompanied by an analytical model. Furthermore, we found that altering the salt concentration of the suspension solution affected the velocity of particles due to the change of dielectric constant and viscosity of the solution. These findings suggest that this technique is suitable for studying particle surface changes and perhaps can be used to dynamically study reaction kinetics at the particle surface.

Although Zika virus (ZIKV) infection is mainly transmitted through mosquito bite, it can also be transmitted through blood transfusion. More than 500 000 cases of ZIKV infection were reported in the Americas from 2015 to 2016. Up till now, over 10 cases of imported ZIKV infection have been reported due to frequent international exchanges in the Shenzhen city of Guangdong Province, China. Unfortunately, there were no data on ZIKV infection in Chinese blood donors because it has not been included in routine screening for volunteer blood donors. As such, we performed a preliminary survey of the prevalence of ZIKV infection among volunteer blood donors in Shenzhen, China, to assess the potential risk of ZIKV infection through transfusion. A total of 9626 blood donor samples were collected and ZIKA RNA was detected by transcription-mediated amplification (TMA) nucleic acid amplification method with the Panther nucleic acid automatic analysis system of Grifols, Spain, including Procleix ZIKV Assay reagent. All the experiments in this study were conducted in accordance with the standard operating procedure of the blood center. Of the 9626 donor blood samples tested, none of these samples was Zika RNA reactive. There was no positive case from ZIKV RNA screening in this preliminary survey. There was no ZIKV presence in blood donors in Shenzhen, China, from this preliminary survey. The potential risk of ZIKV infection by transfusion is low in Shenzhen at this moment. Therefore, there is no need to add ZIKV nucleic acid test as a routine screening for blood donors.

With the rapid development of the digital world, digital rights management (DRM) becomes increasingly important. Multi-Authority Attribute Based Encryption (MA-ABE) schemes provide suitable solutions for flexible fine-grained access control in DRM. However, there are two accountable problems unsolved when applying existing ABE schemes to DRM directly: illegal authorization and key disclosure. Illegal authorization means that some attribute authorities might collude with users and issue attribute keys to unauthorized users illegally. Key disclosure denotes that some users might maliciously expose their attribute keys to the public. Both the above problems could lead to unauthorized users accessing digital content, which is extremely harmful to DRM. To solve these problems, we design a novel MA-ABE scheme based on blockchain. Our scheme ensures that a relevant user could obtain the final decryption attribute key only after all attribute authorities have issued their keys to the blockchain publicly. If a malicious attribute authority issues attribute keys to inappropriate users, the auditor defined in our scheme would detect the malicious behavior. Meanwhile, once some users publish their decryption keys to the public, the auditor is able to transparently trace such users utilizing an incentive mechanism. In addition, we design and implement two smart contracts on Ethereum, called R e c o r d C o n t r a c t and T r a c e C o n t r a c t , which are used to record users’ encrypted attribute keys and encourage participants to trace the owner of disclosed decryption attribute key, respectively. Finally, the security proof and efficiency simulation show that the proposed scheme can be securely and efficiently applied to DRM.