Integrated active and passive control design methodology for the LaRC CSI evolutionary model

A general design methodology to integrate active control with passive damping was demonstrated on the NASA LaRC CSI Evolutionary Model (CEM), a ground testbed for future large, flexible spacecraft. Vibration suppression controllers designed for Line-of Sight (LOS) minimization were successfully implemented on the CEM. A frequency-shaped H2 methodology was developed, allowing the designer to specify the roll-off of the MIMO compensator. A closed loop bandwidth of 4 Hz, including the six rigid body modes and the first three dominant elastic modes of the CEM was achieved. Good agreement was demonstrated between experimental data and analytical predictions for the closed loop frequency response and random tests. Using the Modal Strain Energy (MSE) method, a passive damping treatment consisting of 60 viscoelastically damped struts was designed, fabricated and implemented on the CEM. Damping levels for the targeted modes were more than an order of magnitude larger than for the undamped structure. Using measured loss and stiffness data for the individual damped struts, analytical predictions of the damping levels were very close to the experimental values in the (1-10) Hz frequency range where the open loop model matched the experimental data. An integrated active/passive controller was successfully implemented on the CEM and was evaluated against an active-only controller. A two-fold increase in the effective control bandwidth and further reductions of 30 percent to 50 percent in the LOS RMS outputs were achieved compared to an active-only controller. Superior performance was also obtained compared to a High-Authority/Low-Authority (HAC/LAC) controller

Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension

Recent studies have shown that in response to vascular damage or ischemia, bone marrow-derived endothelial progenitor cells (EPCs) are recruited into the circulation. To investigate whether antihypertensive treatment has an influence on the number of circulating EPCs, patients with essential hypertension were treated either with the angiotensin receptor antagonist telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks. At baseline and after 3 and 6 weeks of treatment, EPCs were identified and quantified by fluorescence-activated cell sorting (FACS) analysis and by their capacity to generate colony-forming units of the endothelial lineage (CFU-EC) in a methylcellulose-based assay. During treatment, patients in the nisoldipine groups, but not in the telmisartan group, showed a significant mobilization of EPCs, which in part had the capacity to generate large-sized colonies comprising more than 1,000 cells. Moreover, a remarkable correlation between the number of CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was observed, thereby providing strong evidence that cells with this phenotype represent functional EPCs. No correlation was found between the numbers of CFU-EC and the blood pressure levels at any time point during the treatment. Hence, nisoldipine-induced mobilization of EPCs might represent a novel mechanism by which this antihypertensive compound independently of its blood pressure-lowering effect contributes to vasoprotection in patients with essential hypertension

A defect in molybdenum cofactor binding causes an attenuated form of sulfite oxidase deficiency

Isolated sulfite oxidase deficiency (ISOD) is a rare recessive and infantile lethal metabolic disorder, which is caused by functional loss of sulfite oxidase (SO) due to mutations of the SUOX gene. SO is a mitochondrially localized molybdenum cofactor (Moco)- and heme-dependent enzyme, which catalyzes the vital oxidation of toxic sulfite to sulfate. Accumulation of sulfite and sulfite-related metabolites such as S-sulfocysteine (SSC) are drivers of severe neurodegeneration leading to early childhood death in the majority of ISOD patients. Full functionality of SO is dependent on correct insertion of the heme cofactor and Moco, which is controlled by a highly orchestrated maturation process. This maturation involves the translation in the cytosol, import into the intermembrane space (IMS) of mitochondria, cleavage of the mitochondrial targeting sequence, and insertion of both cofactors. Moco insertion has proven as the crucial step in this maturation process, which enables the correct folding of the homodimer and traps SO in the IMS. Here, we report on a novel ISOD patient presented at 17 months of age carrying the homozygous mutation NM_001032386.2 (SUOX):c.1097G > A, which results in the expression of SO variant R366H. Our studies show that histidine substitution of Arg366, which is involved in coordination of the Moco-phosphate, causes a severe reduction in Moco insertion efficacy in vitro and in vivo. Expression of R366H in HEK SUOX-/- cells mimics the phenotype of patient's fibroblasts, representing a loss of SO expression and specific activity. Our studies disclose a general paradigm for a kinetic defect in Moco insertion into SO caused by residues involved in Moco coordination resulting in the case of R366H in an attenuated form of ISO

A influência das variações climáticas no módulo de resiliência do subleito de pavimentos testados na área de pesquisas e testes de pavimentos UFRGS/DAER

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A influência das variações climáticas no módulo de resiliência do subleito de pavimentos testados na área de pesquisas e testes de pavimentos UFRGS/DAER

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