Fake-Acknowledgment Attack on ACK-based Sensor Power Schedule for Remote State Estimation

We consider a class of malicious attacks against remote state estimation. A sensor with limited resources adopts an acknowledgement (ACK)-based online power schedule to improve the remote state estimation performance. A malicious attacker can modify the ACKs from the remote estimator and convey fake information to the sensor. When the capability of the attacker is limited, we propose an attack strategy for the attacker and analyze the corresponding effect on the estimation performance. The possible responses of the sensor are studied and a condition for the sensor to discard ACKs and switch from online schedule to offline schedule is provided.Comment: submitted to IEEE CDC 201

Transmission Power Scheduling for Energy Harvesting Sensor in Remote State Estimation

We study remote estimation in a wireless sensor network. Instead of using a conventional battery-powered sensor, a sensor equipped with an energy harvester which can obtain energy from the external environment is utilized. We formulate this problem into an infinite time-horizon Markov decision process and provide the optimal sensor transmission power control strategy. In addition, a sub-optimal strategy which is easier to implement and requires less computation is presented. A numerical example is provided to illustrate the implementation of the sub-optimal policy and evaluation of its estimation performance.Comment: Extended version of article to be published in the Proceedings of the 19th IFAC World Congress, 201

Data-Driven Power Control for State Estimation: A Bayesian Inference Approach

We consider sensor transmission power control for state estimation, using a Bayesian inference approach. A sensor node sends its local state estimate to a remote estimator over an unreliable wireless communication channel with random data packet drops. As related to packet dropout rate, transmission power is chosen by the sensor based on the relative importance of the local state estimate. The proposed power controller is proved to preserve Gaussianity of local estimate innovation, which enables us to obtain a closed-form solution of the expected state estimation error covariance. Comparisons with alternative non data-driven controllers demonstrate performance improvement using our approach

T-cell Checkpoint Pathways Modulate Cell Cycle and Steroid Resistance in T-cell Acute Lymphoblastic Leukaemia

Ph. D. Thesis.T-cell Acute Lymphoblastic Leukaemia (T-ALL) results from the malignant transformation of immature T cells with hallmarks of differentiation blockage and expansive proliferation. The checkpoints during T-cell development are provided by the pre-T-Cell Receptor (pTCR) for β-selection and T-Cell Receptor (TCR) for positive and negative selection. Recurrent gene lesions in proximity to pTCR/TCR are found in T-ALL, such as NOTCH1, FBXW7 and PTEN. Kinases of the pre-B-cell receptor signalling have been validated as drug targets in B-ALL. Whether any critical components of T-cell checkpoint pathways, such as Lymphocyte-specific non-receptor tyrosine Kinase (LCK), play a comparable role in T-ALL remains unclear. A targeted shRNA screen against central components of the pTCR/TCR signalling complex in TALL cell lines in vitro and primary cells in vivo identified an essential role for LCK in cell proliferation and leukaemia propagation. Knockdown of LCK in the cell lines SUPT1, CUTLL1 and MOLT4 revealed a substantial growth defect over time. This was further validated in a competitive assay using MOLT4 in vivo, in which control cells outcompeted LCK knockdown cells in mouse bone marrow, spleen and liver. Phenotypically, knockdown or inhibition of LCK by dasatinib (DAS) impaired cell proliferation by inducing G0/G1 arrest in T-ALL cell lines and patient-derived xenografts (PDXs) with only trivial induction of apoptosis. The sensitivity of T-ALL cell lines to DAS significantly correlated with LCK activation (pY394LCK/LCK). Several cell lines and PDXs were glucocorticoid-resistant in vitro. Interestingly, T-ALL cells were resensitised to dexamethasone (DEX) after LCK knockdown. Correspondingly, DAS reinforced DEX-induced apoptosis. Drug matrix analyses of ten T-ALL cell lines and six PDXs revealed a significant enrichment of DEX/DAS synergy at clinically relevant concentrations. A murine phase ‖-like clinical trial of ten T-ALL PDXs confirmed that DEX/DAS significantly impaired leukaemia engraftment. Engraftment of human leukaemia cells in spleen, bone marrow, and liver was substantially decreased in the DEX/DAS group compared with control or single-drug therapy. In addition, DEX/DAS significantly reduced CNS infiltration of leukaemia cells. The presented research outcomes highlight the crucial role of LCK in T-ALL proliferation and propagation. LCK inhibitor DAS, in conjunction with DEX, reverses steroid resistance and significantly reduces leukaemia propagation in vivo. The DEX/DAS combination might provide a novel therapeutic strategy for refractory and relapsed T-ALL patients.China Scholarship Counci

LQG Control Over SWIPT-enabled Wireless Communication Network

In this paper, we consider using simultaneous wireless information and power transfer (SWIPT) to recharge the sensor in the LQG control, which provides a new approach to prolonging the network lifetime. We analyze the stability of the proposed system model and show that there exist two critical values for the power splitting ratio {\alpha}. Then, we propose an optimization problem to derive the optimal value of {\alpha}. This problem is non-convex but its numerical solution can be derived by our proposed algorithm efficiently. Moreover, we provide the feasible condition of the proposed optimization problem. Finally, simulation results are presented to verify and illustrate the main theoretical results

Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia

T-cell Acute Lymphoblastic Leukemia (T-ALL) is frequently characterized by glucocorticoid (GC) resistance, which is associated with inferior outcomes, thus highlighting the need for novel therapeutic approaches for GC resistant T-ALL. The pTCR/TCR signaling pathways play a critical role in cell fate decisions during physiological thymocyte development, with an interplay between TCR and glucocorticoid receptor (GR) signaling determining the T-lymphocyte selection process. We performed an shRNA screen in vitro and in vivo in T-ALL cell lines and patient derived xenograft (PDX) samples to identify vulnerabilities in the pTCR/TCR pathway and identified a critical role for the kinase LCK in cell proliferation. LCK knockdown or inhibition with dasatinib (DAS) caused cell cycle arrest. Combination of DAS with dexamethasone (DEX) resulted in significant drug synergy leading to cell death. The efficacy of this drug combination was underscored in a randomized phase II-like murine trial, recapitulating an early phase human clinical trial. T-ALL expansion in immunocompromised mice was significantly impaired using this drug combination, relative to mice receiving control vehicle or single drug treatment, highlighting the immediate clinical relevance of this drug combination for high risk T-ALL patients. Our results thus provide a strategy to improve the efficacy of current chemotherapy platforms and circumvent GC resistance

ULK1/2所构成的信号节点除控制细胞自噬外还控制葡萄糖代谢通路

文章简介在细胞感受到环境中营养物质和生长因子的提供量发生改变后,代谢通路的重编程对于维持此时胞内的稳态是非常重要的过程。ULK1和ULK2是传递外界应激信号至自噬发生的重要整合因子。本项研究发现,在缺少氨基酸和生长因子时,ULK1/2能直接磷酸化多个糖酵解相关的酶,包括己糖激酶(HK)、国家自然科学基金重点项目；国家科技部(973课题)；国家基础科学人才培养基金等的经费支持

AMP as a Low-Energy Charge Signal Autonomously Initiates Assembly of AXIN-AMPK-LKB1 Complex for AMPK Activation

The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose-starved or AICAR-treated cells and in cell-free systems supplemented with exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1 colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse liver impaired AMPK activation and caused exacerbated fatty liver after starvation, underscoring an essential role of AXIN in AMPK activation. These findings demonstrate an initiating role of AMP and demonstrate that AXIN directly transmits AMP binding of AMPK to its activation by LKB1, uncovering the mechanistic route for AMP to elicit AMPK activation by LKB1.http://news.xmu.edu.cn/s/13/t/542/22/a9/info139945.ht