New players and new interactions within the natriuretic peptide system : mechanisms and pathophysiological consequences

The natriuretic peptide system plays a pivotal role in the regulation of cardiorenal homeostasis as well as in the pathogenesis of cardiovascular diseases. In this thesis, the biological effects of the newly designed natriuretic peptide (NP) ACNP and mechanisms of the interaction between natriuretic peptide receptor A (NPRA) and B (NPRB) are elucidated. The receptor profiles of different BNPs and degradation profile of hBNP1-42 are also investigated. ACNP stimulates both NPRA and NPRB and thus is more potent and effective compared to human ANP or CNP in stimulating cGMP in primary cells in vitro. In sham-operated mice, 4-week treatment with ACNP exerted similar potency in lowering blood pressure compared to that of ANP or CNP. However, ANP, but not ACNP, ameliorated the myocardial infarction-induced left ventricular dysfunction. The lack of benefit of ACNP might relate to its fast degradation by a still unknown enzyme in mouse serum. The interaction between NPRA and NPRB has been suggested since an impaired cGMP generation upon NP stimulation was observed in NPRA/NPRB co-transfected cells. The inhibitory effect of heterogeneous receptor complexes on natural NP/NPR/cGMP signalling were receptor dose-dependent. The attenuation of the CNP/NPRB/cGMP axis is caused by a blocked formation of NPRB mRNA by NPRA and thus decreasing NPRB quantity on the membrane. The attenuated ANP and BNP signalling may involve conformational changes within the NPRA/NPRB heterodimer, leading to less ligand accessibility or ligand-mediated activation of guanylyl cyclise (GC). Furthermore, different forms of BNP have been studied. The N-terminal truncated BNP (mBNP7-32) and the elongated BNP (mBNP1-45) are able to stimulate NPRA, whereas the C-terminal elongated hBNP1-42 is a poor activator of NPRA. Meanwhile, metabolism of hBNP1-42 on kidney membrane was different to that of lung membrane, suggesting specific peptidase(s) in the kidney being important for renal action of hBNP1-42. Taken together, this thesis gives novel insight into the new players and new interactions in the natriuretic peptide system. It provides potential mechanisms in receptor interplay leading to an impaired cGMP generation. It also opens new directions for the better understanding of cardiovascular diseases and may identify completely new treatment options

A Security Situation Awareness Approach for IoT Software Chain Based on Markov Game Model

Since Internet of Things (IoT) has been widely used in our daily life nowadays, it is regarded as a promising and popular application of the Internet, and has attracted more and more attention. However, IoT is also suffered by some security problems which seriously affect the implementation of IoT system. Similar to traditional software, IoT software is always threated by many vulnerabilities, thus how to evaluate the security situation of IoT software chain becomes a basic requirement. In this paper, A framework of security situation awareness for IoT software chain is proposed, which mainly includes two processes: IoT security situation classification based on support vector machine and security situation awareness based on Markov game model. The proposed method firstly constructs a classification model using support vector machine (IoT) to automatically evaluates the security situation of IoT software chain. Based on the situation classification, we further proposed to adopt Markov model to simulate and predict the next behaviors of participants that involved in IoT system. Additionally, we have designed and developed a security situation awareness system for IoT software chain, the developed system supports the detection of typical IoT vulnerabilities and inherits more than 20 vulnerability detection methods, which shows great potential in IoT system protection

Soft Pilot Reuse and Multi-Cell Block Diagonalization Precoding for Massive MIMO Systems

The users at cell edge of a massive multiple-input multiple-output (MIMO) system suffer from severe pilot contamination, which leads to poor quality of service (QoS). In order to enhance the QoS for these edge users, soft pilot reuse (SPR) combined with multi-cell block diagonalization (MBD) precoding are proposed. Specifically, the users are divided into two groups according to their large-scale fading coefficients, referred to as the center users, who only suffer from modest pilot contamination and the edge users, who suffer from severe pilot contamination. Based on this distinction, the SPR scheme is proposed for improving the QoS for the edge users, whereby a cell-center pilot group is reused for all cell-center users in all cells, while a cell-edge pilot group is applied for the edge users in the adjacent cells. By extending the classical block diagonalization precoding to a multi-cell scenario, the MBD precoding scheme projects the downlink transmit signal onto the null space of the subspace spanned by the inter-cell channels of the edge users in adjacent cells. Thus, the inter-cell interference contaminating the edge users' signals in the adjacent cells can be efficiently mitigated and hence the QoS of these edge users can be further enhanced. Our theoretical analysis and simulation results demonstrate that both the uplink and downlink rates of the edge users are significantly improved, albeit at the cost of the slightly decreased rate of center users.Comment: 13 pages, 12 figures, accepted for publication in IEEE Transactions on Vehicular Technology, 201

Adaptive hybrid precoding for multiuser massive MIMO

Hybrid precoding (HP) is widely utilized in millimeter wave-based massive MIMO systems with significantly reduced radio frequency (RF) chains, but it requires a large number of analog phase shifters (APSs) and RF adders to realize the connection between RF chains and antenna elements. In this letter, an adaptive hybrid precoding (AHP) is proposed to approach the performance of the conventional HP with reduced complexity. Different from the conventional HP where each antenna is connected to all RF chains through APSs and RF adders, the proposed AHP connects each antenna with only one RF chain through an adaptive connection network. This adaptive connection network and the phases of APSs are jointly designed, which is formulated as an optimization problem to maximize the users' average downlink achievable rate. Moreover, a multiuser adaptive analog precoding (MU-AAP) algorithm is proposed to provide a near-optimal solution to this joint-design problem. Simulation results verify the performance gain of the proposed AHP in typical multiuser massive MIMO scenario