Copper may play an important role in the brain in aging and neurodegenerative diseases. We compare the active Cu uptake, Cu-containing enzyme levels, and total Cu distribution in the brains of young and aging mice. (67)Cu was administered intravenously to 2, 7-9, and 14 month old mice. Active uptake of (67)Cu in the brain was measured at 24 h by digital phosphor autoradiography. Cerebral superoxide dismutase-1 (SOD-1) and cytochrome-C oxidase subunit-1 (CCO-1) levels were analyzed by immunohistochemistry. The total Cu distribution in brain section was determined by imaging laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In aging mice, active (67)Cu uptake and SOD-1 levels were significantly decreased in the brain, whereas blood (67)Cu and CCO-1 levels were similar for all mice, irrespective of age. Paradoxically, global Cu cerebral content was increased in aged mice, suggesting that regulation of active Cu uptake by the brain may be linked to total Cu levels in an attempt to maintain Cu homeostasis. However, focal areas of both decreased Cu uptake and Cu content were noted in the striatum and ventral cortex in aging mice. These focal areas of Cu deficit correspond to the regions of greatest reduction in SOD-1 in the aged mice. In aging, dysregulated Cu homeostasis may result in decreased SOD-1 levels, which may contribute to oxidative vulnerability of the aging brain. This study illustrates the importance of a multi-modality approach in studying the biodistribution and homeostasis of Cu in the brain.

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Introduction Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18F-fluoro-2-deoxyglucose (18F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14C-2DG uptake in activated neutrophils. Methods Lung uptake of 18F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 hours following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results Significant uptake of 18F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion Systemic endotoxin-induced ALI results in very early and progressive uptake of 18F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care 18F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14C-2DG uptake in activated neutrophils. 18F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS.

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During the condition monitoring of a planetary gearbox, features are extracted from raw data for a fault diagnosis. However, different features have different sensitivity for identifying different fault types, and thus, the selection of a sensitive feature subset from an entire feature set and retaining as much of the class discriminatory information as possible has a directly effect on the accuracy of the classification results. In this paper, an improved hybrid feature selection technique (IHFST) that combines a distance evaluation technique (DET), Pearson's correlation analysis, and an ad hoc technique is proposed. In IHFST, a temporary feature subset without irrelevant features is first selected according to the distance evaluation criterion of DET, and the Pearson's correlation analysis and ad hoc technique are then employed to find and remove redundant features in the temporary feature subset, respectively, and hence, a sensitive feature subset without irrelevant or redundant features is selected from the entire feature set. Further, the k-means clustering method is applied to classify the different kinds of health conditions. The effectiveness of the proposed method was validated through several experiments carried out on a planetary gearbox with incipient cracks seeded in the tooth root of the sun gear, planet gear, and ring gear. The results show that the proposed method can successfully distinguish the different health conditions of a planetary gearbox, and achieves a better classification performance than other methods. This study proposes a sensitive feature subset selection method that achieves an obvious improvement in terms of the accuracy of the fault classification.

Inactivation of polyphenol oxidase (PPO) and lipoxygenase (LOX) by pulsed electric fields (PEFs) has been investigated using a coaxial treatment chamber. Circular dichroism (CD) and fluorescence analysis have been used to study conformation changes in the protein. The experimental results show that PPO and LOX can be effectively deactivated by the PEF treatment and that the effect on PPO and LOX increases with the increase of the applied electric field and the number of pulses. The activity of PPO and LOX can be reduced by 69 and 88% when fields of 24 kV/cm were applied for 320 and 962 ls, respectively. The CD analysis showed that the PEF treatment caused a loss of a-helix and increase of b-sheet content, indicating that conformation changes occur in the secondary structure of the PPO and LOX enzymes. The fluorescence intensity of LOX increases after the PEF treatment while, at the same time, increases in the applied electric field increases the intensity of the fluorescence emitted. These results prove the occurrence of local tertiary structure changes in the LOX protein.

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