Detection and diagnosis of parameters change in linear system using time-frequency transformation

A systematic optimization of the Cohen class time-frequency transformation for detecting the parameters change is developed. The local moments approach to change detection is proposed and a general formula for the local moments is derived. The optimal kernel functions of the time-frequency transformation are determined based on the combined criteria of maximum sensitivity with respect to parameters change and minimum distortion of physical interpretation of the local moments. The sensitivity of the local moment with respect to a certain kind of inputs is analyzed and a most "convenient" and a "worst" input are identified. The results are presented in the form of the case studies for detecting parameters change in simple linear systems

Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes

This study was performed to investigate the transduction of a full-length superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat) into human chondrocytes, and to determine the regulatory function of transduced Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD expression vector was constructed to express the basic domain of HIV-1 Tat as a fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were cultured in both a monolayer and an explant. For the transduction of fusion proteins, cells/explants were treated with a variety of concentrations of fusion proteins. The transduced protein was detected by fluorescein labeling, western blotting and SOD activity assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression was assessed by the Griess reaction and reverse transcriptase PCR, respectively. Tat-SOD was successfully delivered into both the monolayer and explant cultured chondrocytes, whereas the control SOD was not. The intracellular transduction of Tat-SOD into cultured chondrocytes was detected after 1 hours, and the amount of transduced protein did not change significantly after further incubation. SOD enzyme activity increased in a dose-dependent manner. NO production and iNOS mRNA expression, in response to IL-1 stimulation, was significantly down-regulated by pretreatment with Tat-SOD fusion proteins. This study shows that protein delivery employing the Tat-protein transduction domain is feasible as a therapeutic modality to regulate catabolic processes in cartilage. Construction of additional Tat-fusion proteins that can regulate cartilage metabolism favorably and application of this technology in in vivo models of arthritis are the subjects of future studies

Predictive Coding Strategies for Developmental Neurorobotics

In recent years, predictive coding strategies have been proposed as a possible means by which the brain might make sense of the truly overwhelming amount of sensory data available to the brain at any given moment of time. Instead of the raw data, the brain is hypothesized to guide its actions by assigning causal beliefs to the observed error between what it expects to happen and what actually happens. In this paper, we present a variety of developmental neurorobotics experiments in which minimalist prediction error-based encoding strategies are utilize to elucidate the emergence of infant-like behavior in humanoid robotic platforms. Our approaches will be first naively Piagian, then move onto more Vygotskian ideas. More specifically, we will investigate how simple forms of infant learning, such as motor sequence generation, object permanence, and imitation learning may arise if minimizing prediction errors are used as objective functions

Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway.

YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study establishes a molecular mechanism and functional significance of AMPK in linking cellular energy status to the Hippo-YAP pathway