Remote Sensing for a Lining Integrated Active Structural Acoustic Control System

In the framework of the EU project ACASIAS an aircraft sidewall panel (lining) with structurally integrated actuators and sensors is developed. Each lining has a digital unit which samples the sensor signals, performs filtering operations and supplies the actuators with control signals. The whole system makes up an active structural acoustic control system aiming at the reduction of low-frequency multi-tonal aircraft interior noise. The novelty of this approach compared to past implementations of active noise control (ANC) systems in aircraft is its modularity. Each so-called smart lining is autonomous in the sense that it processes only structural sensor data from its own integrated sensors. The use of external microphones for error sensing is avoided because this conflicts with the modularity of the smart lining. Hence, one important design task is the replacement of the physical error microphones by the integrated structural sensors and an acoustic filter (observer) running on the digital unit. This method, which is called the remote microphone technique for active control, has never been applied to an aircraft interior structure so far. The detailed design of the smart lining module comprises several steps which are taken within work package 3 of the ACASIAS project. Experimental data of an aircraft typical double panel system is captured in a sound transmission loss facility. The system is excited with a loudspeaker array placed directly in front of the fuselage structure. Different acoustic load cases are used for the definition of the sensors and the actuators. A multi-tonal excitation with high sound pressure level is relevant for the actuator dimensioning and a broadband excitation with multiple independent sound sources is relevant for the sensor definition. 19 accelerometers are mounted on the lining and 20 microphones are placed in front of it. All sensor signals are sampled simultaneously for deterministic and broadband load cases. The lining is equipped with two inertial mass actuators which are used for the active control. Measured frequency response functions of actuators at 39 positions are used for the optimization of the actuator locations. The measurement data is also used for the derivation of an observer and for the simulation of a smart lining with remote microphones. In this contribution, the steps undertaken for the detailed design will be described and simulation results of the noise reduction performance of the smart lining with remote microphones will be presented

Towards a Lining Integrated Active Structural Acoustic Control System

For future aircraft counter-rotating open rotor (CROR) engines are a promising technology to reduce their CO2 footprint. Since the contribution of CROR engines to the cabin noise is higher than for jet engines, new strategies for the reduction of noise transmissions for frequency bands below 500 Hz are necessary. Active structural acoustic control (ASAC) systems are capable to reduce sound transmission of lining structures in this bandwidth. Sensors measure the vibrations of the lining to estimate its sound emission into the cabin. Based on these signals a controller calculates force signals for actuators on the lining. The actuator forces change the vibration behaviour of the lining in order to reduce its sound emission. For the realization of such a system in a real aircraft, manufacturing and maintenance issues have to be addressed. Within work package 3 of the EU project ACASIAS an aircraft lining with an integrated ASAC system is developed. The size of the lining is app. 1300 x 1690 mm2 (W x H) and it is simply curved. The radius of 2980 mm makes it relevant for a twin-aisle aircraft like the Airbus A350. The focus of research activities lies on the integration of components and the industrial manufacturing process of the lining. The components to be integrated are sensors, actuators and the corresponding wiring. A concept is proposed where each actuator and sensor is encapsulated in a kind of insert. The inserts smoothly integrate into the manufacturing process of the lining while they protect the actuators and sensors from humidity, dust, etc. The maintenance aspect is covered by the option to change each actuator or sensor upon insert level. The integrated wiring of the lining is left unaffected during an actuator or sensor replacement since connectors in each insert allow a nearly tool-free assembly/disassembly. In this paper the progress of work package 3 is presented at a detailed design review (DDR) stage. Finally, the lining will be manufactured and equipped with a full ASAC system. Experiments will be conducted in the acoustic transmission loss facility at the DLR

Growth rates and the prevalence and progression of scoliosis in short-statured children on Australian growth hormone treatment programmes

STUDY DESIGN AND AIM: This was a longitudinal chart review of a diverse group (cohort) of patients undergoing HGH (Human Growth Hormone) treatment. Clinical and radiological examinations were performed with the aim to identify the presence and progression of scoliosis. METHODS AND COHORT: 185 patients were recruited and a database incorporating the age at commencement, dose and frequency of growth hormone treatment and growth charts was compiled from their Medical Records. The presence of any known syndrome and the clinical presence of scoliosis were included for analysis. Subsequently, skeletally immature patients identified with scoliosis were followed up over a period of a minimum four years and the radiologic type, progression and severity (Cobb angle) of scoliosis were recorded. RESULTS: Four (3.6%) of the 109 with idiopathic short stature or hormone deficiency had idiopathic scoliosis (within normal limits for a control population) and scoliosis progression was not prospectively observed. 13 (28.8%) of 45 with Turner syndrome had scoliosis radiologically similar to idiopathic scoliosis. 11 (48%) of 23 with varying syndromes, had scoliosis. In the entire cohort, the growth rates of those with and without scoliosis were not statistically different and HGH treatment was not ceased because of progression of scoliosis. CONCLUSION: In this study, there was no evidence of HGH treatment being responsible for progression of scoliosis in a small number of non-syndromic patients (four). An incidental finding was that scoliosis, similar to the idiopathic type, appears to be more prevalent in Turner syndrome than previously believed

Continuous Quinacrine Treatment Results in the Formation of Drug-Resistant Prions

Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR0/0 mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 µM of quinacrine in their brains without acute toxicity. PrPSc levels in the brains of prion-inoculated MDR0/0 mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrPSc levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR0/0 mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrPSc levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrPSc that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR0/0 mice. From these data, we propose that quinacrine eliminates a specific subset of PrPSc conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs

Pharmacokinetics of Quinacrine Efflux from Mouse Brain via the P-glycoprotein Efflux Transporter

The lipophilic cationic compound quinacrine has been used as an antimalarial drug for over 75 years but its pharmacokinetic profile is limited. Here, we report on the pharmacokinetic properties of quinacrine in mice. Following an oral dose of 40 mg/kg/day for 30 days, quinacrine concentration in the brain of wild-type mice was maintained at a concentration of ∼1 µM. As a substrate of the P-glycoprotein (P-gp) efflux transporter, quinacrine is actively exported from the brain, preventing its accumulation to levels that may show efficacy in some disease models. In the brains of P-gp–deficient Mdr10/0 mice, we found quinacrine reached concentrations of ∼80 µM without any signs of acute toxicity. Additionally, we examined the distribution and metabolism of quinacrine in the wild-type and Mdr10/0 brains. In wild-type mice, the co-administration of cyclosporin A, a known P-gp inhibitor, resulted in a 6-fold increase in the accumulation of quinacrine in the brain. Our findings argue that the inhibition of the P-gp efflux transporter should improve the poor pharmacokinetic properties of quinacrine in the CNS

Differential Proteome Analysis of Bone Marrow Mesenchymal Stem Cells from Adolescent Idiopathic Scoliosis Patients

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. The cause and pathogenesis of scoliosis and the accompanying generalized osteopenia remain unclear despite decades of extensive research. In this study, we utilized two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) to analyze the differential proteome of bone marrow mesenchymal stem cells (BM-MSCs) from AIS patients. In total, 41 significantly altered protein spots were detected, of which 34 spots were identified by MALDI-TOF/TOF analysis and found to represent 25 distinct gene products. Among these proteins, five related to bone growth and development, including pyruvate kinase M2, annexin A2, heat shock 27 kDa protein, γ-actin, and β-actin, were found to be dysregulated and therefore selected for further validation by Western blot analysis. At the protein level, our results supported the previous hypothesis that decreased osteogenic differentiation ability of MSCs is one of the mechanisms leading to osteopenia in AIS. In summary, we analyzed the differential BM-MSCs proteome of AIS patients for the first time, which may help to elucidate the underlying molecular mechanisms of bone loss in AIS and also increase understanding of the etiology and pathogenesis of AIS