TLCD Parametric Optimization for the Vibration Control of Building Structures Based on Linear Matrix Inequality

Passive liquid dampers have been used to effectively reduce the dynamic response of civil infrastructures subjected to earthquakes or strong winds. The design of liquid dampers for structural vibration control involves the determination of the optimal parameters. This paper presents an optimal design methodology for tuned liquid column dampers (TLCDs) based on the H∞ control theory. A practical structure, Dalian Xinghai Financial Business Building, is used to illustrate the feasibility of the optimal procedure. The model of structure is built by the finite element method and simplified to the lumped mass model. To facilitate the design of TLCDs, the TLCD parametric optimization problem is transferred to the feedback controller design problem. Through the bounded real lemma, an optimization problem with bilinear matrix inequality (BMI) constraints is constructed to design a static output feedback H∞ controller. Iterative linear matrix inequality method is employed and it added some value range constraints to solve the BMI problem. After the TLCD parameters are optimized, the responses of displacement and acceleration in frequency domain and time domain are compared for the structure with and without TLCD. It is validated that the TLCD with the optimized parameters can make the structure satisfy the need for safety and comfort

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice

Background: Methylphenidate (MPH) is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria for these disorders. MPH has also been misused as a cognitive enhancer and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell number and gene expression in the basal ganglia. Methodology/Principal Findings: Through the use of stereological counting methods, we observed a significant reduction (~20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10 mg/kg MPH. This dosage of MPH also induced a significant increase in the number of activated microglia in the SNpc. Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigra (SN) were observed with both acute and chronic dosing of 10 mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-α in the striatum, although these were seen only at an acute dose of 10 mg/kg and not following chronic dosing. Conclusion: Collectively, our results suggest that chronic MPH usage in mice at doses spanning the therapeutic range in humans, especially at prolonged higher doses, has long-term neurodegenerative consequences

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.

Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome. Activation of eukaryotic gene transcription involves the coordination of a multitude of transcription factors and cofactors on regulatory DNA sequences such as promoters and enhancers and on the chromatin structure containing these elements 1-3 . Promoters are located at the 5¢ ends of genes immediately surrounding the transcriptional start site (TSS) and serve as the point of assembly of the transcriptional machinery and initiation of transcription 4 . Enhancers contribute to the activation of their target genes from positions upstream, downstream or within a target or neighboring gene Recent investigations using chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) experiments have described the chromatin architecture of transcriptional promoters in yeast, fly and mammalian systems 9 . In a manner largely conserved across species, active promoters are marked by acetylation of various residues of histones H3 and H4 and methylation of H3K4, particularly trimethylation of this residue. Nucleosome depletion is also a general characteristic of active promoters in yeast and flies, although this feature remains to be thoroughly examined in mammalian systems. Although some studies suggest that distal regulatory elements like enhancers may be marked by similar histone modification patterns 10-13 , the distinguishing chromatin features of promoters and enhancers have yet to be determined, hindering our understanding of a predictive histone code for different classes of regulatory elements. Here, we present high-resolution maps of multiple histone modifications and transcriptional regulators in 30 Mb of the human genome, demonstrating that active promoters and enhancers are associated with distinct chromatin signatures that can be used to predict these regulatory elements in the human genome. RESULTS Chromatin architecture and transcription factor localization We performed ChIP-chip analysis 14 to determine the chromatin architecture along 44 human loci selected by the ENCODE consortium as common targets for genomic analysis 15 , totaling 30 Mb

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice

Background: Methylphenidate (MPH) is a psychostimulant that exerts its pharmacological effects via preferential blockade of the dopamine transporter (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine levels in the synapse. Clinically, methylphenidate is prescribed for the symptomatic treatment of ADHD and narcolepsy; although lately, there has been an increased incidence of its use in individuals not meeting the criteria for these disorders. MPH has also been misused as a ‘‘cognitive enhancer’ ’ and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell number and gene expression in the basal ganglia. Methodology/Principal Findings: Through the use of stereological counting methods, we observed a significant reduction (,20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10 mg/kg MPH. This dosage of MPH also induced a significant increase in the number of activated microglia in the SNpc. Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Unbiased gene screening employing Affymetrix GeneChipH HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigr

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL).1,2 Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases, and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia, in which DUX4 deregulation results in loss-of-function of ERG, either by deletion or induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

A Mesoscopic Viewpoint on Slurry Penetration and Pressure Transfer Mechanisms for Slurry Shield Tunneling

The penetration characteristics of the slurry and the support pressure transfer mechanisms are critical to the tunnel face stability control during a mechanized excavation. In this paper, numerical calculations coupling computational fluid dynamics (CFD) with the discrete element method (DEM) are carried out to simulate sand column penetration tests considering different particle size ratios. The reasonableness of the numerical model is verified by comparing the variation patterns of the soil permeability coefficients monitored in the numerical tests with the results of existing laboratory tests. The mesoscopic transport characteristics of the slurry particles in the sand soil pores are considered based on numerical tests, while the slurry support effects corresponding to different penetration types are evaluated. Three main basic types of slurry infiltration are observed due to the different ratios of slurry particle size over soil pore size. For the first penetration type, the slurry particles are accumulated and able to form a supporting filter cake. The slurry support is effective because of the significant pressure drop generated on both sides of the filter cake. For the second penetration type, both a filter cake and an infiltration zone are present. A dense filling network is formed between the filter cake and the penetration zone. The third type corresponds to a purely penetration zone. An effective impermeable filling network cannot be formed, and the slurry support effect is not obvious. The development of slurry penetration distance shows an obvious time effect; the farther the penetration distance, the larger the slurry filtration loss, and the worse the transformation effect of slurry support pressure

Fault Tolerant Control for Civil Structures Based on LMI Approach

The control system may lose the performance to suppress the structural vibration due to the faults in sensors or actuators. This paper designs the filter to perform the fault detection and isolation (FDI) and then reforms the control strategy to achieve the fault tolerant control (FTC). The dynamic equation of the structure with active mass damper (AMD) is first formulated. Then, an estimated system is built to transform the FDI filter design problem to the static gain optimization problem. The gain is designed to minimize the gap between the estimated system and the practical system, which can be calculated by linear matrix inequality (LMI) approach. The FDI filter is finally used to isolate the sensor faults and reform the FTC strategy. The efficiency of FDI and FTC is validated by the numerical simulation of a three-story structure with AMD system with the consideration of sensor faults. The results show that the proposed FDI filter can detect the sensor faults and FTC controller can effectively tolerate the faults and suppress the structural vibration

A Modified D-K Iteration Approach for the Decentralized ℋ∞ Control of Civil Structures with Parametric Uncertainties

This paper presents a robust decentralized ℋ∞ controller design method to suppress the vibration of civil structures with the consideration of parametric uncertainties. The decentralized ℋ∞ controller design is motivated by the double homotopy approach, which approximates the bilinear matrix inequality (BMI) derived from bounded real lemma to linear matrix inequality (LMI), and gradually deforms a centralized controller to a decentralized controller. The centralized ℋ∞ controller can be designed for the civil structures with the parametric uncertainties through D-K iteration method in μ synthesis, which can consider the diagonal block pattern of the uncertain matrix. This paper combines the double homotopy approach and D-K iteration method to design the robust decentralized ℋ∞ controller for the civil structures with parametric uncertainties. The proposed method is validated numerically with a four-story building example