ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.
For secure communication between any two neighboring sensing devices on the Internet of Things (IoT) environment, it is essential to design a secure device access control and key agreement protocol, in which the two phases, namely, ''node authentication'' and ''key agreement'' are involved. While the node authentication allows two sensing devices to authenticate each other using their own pre-loaded secret credentials in memory, the key agreement phase permits to establish a secret key between them if the mutual authentication is successful. In this paper, we propose a new certificate-based ''lightweight access control and key agreement protocol in the IoT environment, called LACKA-IoT,'' that utilizes the elliptic curve cryptography (ECC) along with the ''collision-resistant one-way cryptographic hash function.'' Through a detailed security analysis using the formal security under the ''Real-Or-Random (ROR) model,'' informal (non-mathematical) security analysis, and formal security verification using the broadly used ''Automated Validation of Internet Security Protocols and Applications (AVISPA)'' tool, we show that the LACKA-IoT can protect various known attacks that are needed for a secure device access control mechanism in the IoT. Furthermore, through a comparative study of the LACKA-IoT and other relevant schemes, we show that there is a better tradeoff among the security and functionality features and communication and computational costs of the LACKA-IoT as compared to other schemes. Finally, the ''practical demonstration using the NS2 simulation'' has been carried out on the LACKA-IoT to measure various network parameters. INDEX TERMS Internet of Things (IoT), smart devices, device access control, key agreement, security, AVISPA.
The Internet of Medical Things (IoMT) is a kind of connected infrastructure of smart medical devices along with software applications, health systems and services. These medical devices and applications are connected to healthcare systems through the Internet. The Wi-Fi enabled devices facilitate machine-to-machine communication and link to the cloud platforms for data storage. IoMT has the ability to make accurate diagnoses, with fewer mistakes and lower costs of care. IoMT with smartphone applications permits the patients to exchange their health related confidential and private information to the healthcare experts (i.e., doctors) for the better control of diseases, and also for tracking and preventing chronic illnesses. Due to insecure communication among the entities involved in IoMT, an attacker can tamper with the confidential and private health related information for example an attacker can not only intercept the messages, but can also modify, delete or insert malicious messages during communication. To deal this sensitive issue, we design a novel blockchain enabled authentication key agreement protocol for IoMT environment, called BAKMP-IoMT. BAKMP-IoMT provides secure key management between implantable medical devices and personal servers and between personal servers and cloud servers. The legitimate users can also access the healthcare data from the cloud servers in a secure way. The entire healthcare data is stored in a blockchain maintained by the cloud servers. A detailed formal security including the security verification of BAKMP-IoMT using the widely-accepted Automated Validation of Internet Security Protocols and Applications (AVISPA) tool is performed to demonstrate its resilience against the different types of possible attack. The comparison of BAKMP-IoMT with relevant existing schemes is conducted which identifies that the proposed system furnishes better security and functionality, and also needs low communication and computational costs as compared to other schemes. Finally, the simulation of BAKMP-IoMT is conducted to demonstrate its impact on the performance parameters.
Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.’s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.
The stress produced by the coupling of reactive oxygen species (ROS) and endoplasmic reticulum (ER) has been explored extensively, but little is known regarding their roles in the early development of mammalian embryos. Here, we demonstrated that the early development of in vitro-produced (IVP) bovine embryos was governed by the cooperative action between ROS and ER stress. Compared with the tension produced by 5% O2, 20% O2 significantly decreased the blastocyst formation rate and cell survival, which was accompanied by increases in ROS and in levels of sXBP-1 transcript, which is an ER stress indicator. In addition, treatment with glutathione (GSH), a ROS scavenger, decreased ROS levels, which resulted in increased blastocyst formation and cell survival rates. Importantly, levels of sXBP-1 and ER stress-associated transcripts were reduced by GSH treatment in developing bovine embryos. Consistent with this observation, tauroursodeoxycholate (TUDCA), an ER stress inhibitor, improved blastocyst developmental rate, trophectoderm proportion, and cell survival. Moreover, ROS and sXBP-1 transcript levels were markedly decreased by supplementation with TUDCA, suggesting a possible mechanism governing the mutual regulation between ROS and ER stress. Interestingly, knockdown of XBP-1 transcripts resulted in both elevation of ROS and decrease of antioxidant transcripts, which ultimately reduced in vitro developmental competence of bovine embryos. Based on these results, in vitro developmental competence of IVP bovine embryos was highly dependent on the coupled response between oxidative and ER stresses. These results increase our understanding of the mechanism(s) governing early embryonic development and may improve strategies for the generation of IVP embryos with high developmental competence.
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