The Performance of Observer-based Residuals for Detecting Intermittent Faults: The Limitations

AbstractIn this paper a broad nonlinear system is considered. Attention is focused upon both performance of a high-gain observer-based residual and the investigation of residual effectiveness for detecting faults in actuators/components. Residual performances for different fault positions and various system complexities are compared. Both qualitative and quantitative evidence for selected fault positions indicated the performance and the effectiveness of the residuals decrease by ascending the system complexity. The poor performance of residuals in the more complex system may cause No Fault Found (NFF). The methods may be extended to the more general class of nonlinear systems and different observers. Efficiency of the proposed approach is demonstrated through the intermittent failure case in a vehicle suspension system

Economic evaluation of mental health effects of flooding using Bayesian networks

The appraisal of appropriate levels of investment for devising flooding mitigation and to support recovery interventions is a complex and challenging task. Evaluation must account for social, political, environmental and other conditions, such as flood state expectations and local priorities. The evaluation method should be able to quickly identify evolving investment needs as the incidence and magnitude of flood events continue to grow. Quantification is essential and must consider multiple direct and indirect effects on flood related outcomes. The method proposed is this study is a Bayesian network, which may be used ex-post for evaluation, but also ex-ante for future assessment, and near real-time for the reallocation of investment into interventions. The particular case we study is the effect of flood interventions upon mental health, which is a gap in current investment analyses. Natural events such as floods expose people to negative mental health disorders including anxiety, distress and post-traumatic stress disorder. Such outcomes can be mitigated or exacerbated not only by state funded interventions, but by individual and community skills and experience. Success is also dampened when vulnerable and previously exposed victims are affected. Current measures evaluate solely the effectiveness of interventions to reduce physical damage to people and assets. This paper contributes a design for a Bayesian network that exposes causal pathways and conditional probabilities between interventions and mental health outcomes as well as providing a tool that can readily indicate the level of investment needed in alternative interventions based on desired mental health outcomes

Computing Dependencies between DCT Coefficients for Natural Steganography in JPEG Domain

International audienc

Targeted Reinforcement of Macrophage Reprogramming Toward M2 Polarization by IL-4-Loaded Hyaluronic Acid Particles

Alteration of macrophage polarization from inflammatory (M1) to anti-inflammatory (M2) phenotype can have striking implications for the regeneration of injured tissues, treatment of inflammatory diseases, and relief of autoimmune disorders. Although certain cytokines like interleukin (IL)-4 and IL-13 are capable of inducing M2 macrophage polarization, their therapeutic potential in vivo is suffering from low efficacy due to their instability and poor access to target cells. Here, we report the synthesis of IL-4-loaded hyaluronic acid (HA) particle for the targeted delivery of cytokines through the high affinity of HA to CD44 receptors of macrophages. HA carriers composed of low, middle, and high molecular weight (MW) polymers were synthesized using divinyl sulfone (DVS) cross-linking. The MW of HA had a negligible effect on the physicochemical properties and biocompatibility of the macrophages, but as an indicative of M2 polarization, a significant change in the arginase-1 (Arg-1) activity, TNF-a release, and IL-10 secretion was observed for the HA particles prepared with high MW polymers. Therefore, these particles were loaded with IL-4 for simultaneous macrophage targeting and M1 to M2 reprogramming, evidenced by a remarkable increase in the Arg-1 to iNOS ratio, as well as CD163 and CD206 upregulation in the M1 macrophages, which were initially triggered by lipopolysaccharide and interferon-y.M.-A.S. acknowledges financial support from Academy of Finland (Decision no. 317316), Iran’s National Elites Foundation and Iran Nanotechnology Initiative Council. T.B.-R. acknowledges financial support from the Fundação para a Ciência e a Tecnologia (Grant no. SFRH/BD/110859/2015). Financial support from the FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through the FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) is acknowledged. H.A.S. acknowledges financial support from the Sigrid Jusélius Foundation (Decision no. 4704580), the Helsinki Institute of Life Science, and the Academy of Finland (Decision no. 1317042)

Enhancing reliability and efficiency for real-time robust adaptive steganography using cyclic redundancy check codes

The development of multimedia and deep learning technology bring new challenges to steganography and steganalysis techniques. Meanwhile, robust steganography, as a class of new techniques aiming to solve the problem of covert communication under lossy channels, has become a new research hotspot in the field of information hiding. To improve the communication reliability and efficiency for current real-time robust steganography methods, a concatenated code, composed of Syndrome–Trellis codes (STC) and cyclic redundancy check (CRC) codes, is proposed in this paper. The enhanced robust adaptive steganography framework proposed is this paper is characterized by a strong error detection capability, high coding efficiency, and low embedding costs. On this basis, three adaptive steganographic methods resisting JPEG compression and detection are proposed. Then, the fault tolerance of the proposed steganography methods is analyzed using the residual model of JPEG compression, thus obtaining the appropriate coding parameters. Experimental results show that the proposed methods have a significantly stronger robustness against compression, and are more difficult to be detected by statistical based steganalytic methods

High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma

NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.Peer reviewe