Statistical Method Based Waveform Optimization in Collocated MIMO Radar Systems

Multiple-input multiple-output (MIMO) radar has acquired considerable attention as it offers an additional degree of freedom which results in performance gains when contrasted with the regular single antenna element radar system. Waveform optimization in MIMO radar is essential as it can offer tremendous improvements in target detection which are quantified in terms of reductions in the symbol error rate and improvements in target detection probability. In this work, we foster a strategy for the optimization of transmitter and receiver waveform in a collocated MIMO radar by only considering the second order statistics, thus relaxing the information of the instantaneous target states. Our contributions are primarily two-fold. First, we find a closed-form expression of the outage probability of an unknown target under clutter environment. For this prospect, we model the signal-to-interference-plus-noise ratio in a canonical quadratic structure, and then utilize the modern residue theory approach to characterize the distribution function. Secondly, we propose constrained and unconstrained optimization problems for the reduction in outage probability using algorithmic techniques such as interior-point, sequential-quadratic programming, and the active-set method for the optimization of the transmitter and receiver waveform. We also provide simulated re-enactments to validate our hypothetical deductions

Statistical Method Based Waveform Optimization in Collocated MIMO Radar Systems

Multiple-input multiple-output (MIMO) radar has acquired considerable attention as it offers an additional degree of freedom which results in performance gains when contrasted with the regular single antenna element radar system. Waveform optimization in MIMO radar is essential as it can offer tremendous improvements in target detection which are quantified in terms of reductions in the symbol error rate and improvements in target detection probability. In this work, we foster a strategy for the optimization of transmitter and receiver waveform in a collocated MIMO radar by only considering the second order statistics, thus relaxing the information of the instantaneous target states. Our contributions are primarily two-fold. First, we find a closed-form expression of the outage probability of an unknown target under clutter environment. For this prospect, we model the signal-to-interference-plus-noise ratio in a canonical quadratic structure, and then utilize the modern residue theory approach to characterize the distribution function. Secondly, we propose constrained and unconstrained optimization problems for the reduction in outage probability using algorithmic techniques such as interior-point, sequential-quadratic programming, and the active-set method for the optimization of the transmitter and receiver waveform. We also provide simulated re-enactments to validate our hypothetical deductions

A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins

Abstract Among therapeutic proteins, cytokines and growth factors have great potential for regenerative medicine applications. However, these molecules have encountered limited clinical success due to low effectiveness and major safety concerns, highlighting the need to develop better approaches that increase efficacy and safety. Promising approaches leverage how the extracellular matrix (ECM) controls the activity of these molecules during tissue healing. Using a protein motif screening strategy, we discovered that amphiregulin possesses an exceptionally strong binding motif for ECM components. We used this motif to confer the pro-regenerative therapeutics platelet-derived growth factor-BB (PDGF-BB) and interleukin-1 receptor antagonist (IL-1Ra) a very high affinity to the ECM. In mouse models, the approach considerably extended tissue retention of the engineered therapeutics and reduced leakage in the circulation. Prolonged retention and minimal systemic diffusion of engineered PDGF-BB abolished the tumour growth-promoting adverse effect that was observed with wild-type PDGF-BB. Moreover, engineered PDGF-BB was substantially more effective at promoting diabetic wound healing and regeneration after volumetric muscle loss, compared to wild-type PDGF-BB. Finally, while local or systemic delivery of wild-type IL-1Ra showed minor effects, intramyocardial delivery of engineered IL-1Ra enhanced cardiac repair after myocardial infarction by limiting cardiomyocyte death and fibrosis. This engineering strategy highlights the key importance of exploiting interactions between ECM and therapeutic proteins for developing effective and safer regenerative therapies

Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice

Abstract Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages. Specially, Tregs lead to a reduction in pro-inflammatory Ly6CHi CCR2+ monocytes/macrophages accompanied by a rapid shift of macrophages towards a pro-repair phenotype. Additionally, exogenous Treg-derived factors, including nidogen-1 and IL-10, along with a decrease in cardiac CD8+ T cell number, mediate the reduction of the pro-inflammatory monocyte/macrophage subset in the heart. Supporting the pivotal role of IL-10, exogenous Tregs knocked out for IL-10 lose their pro-repair capabilities. Together, this study highlights the beneficial use of a Treg-based therapeutic approach for cardiac repair with important mechanistic insights that could facilitate the development of novel immunotherapies for MI