The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remain poorly understood. Here, we generate a metabolome atlas of the aging wildtype mouse brain from 10 anatomical regions spanning from adolescence to old age. We combine data from three assays and structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between brain regions or age groups, but not by sex. A shift in sphingolipid patterns during aging related to myelin remodeling is accompanied by large changes in other metabolic pathways. Functionally related brain regions (brain stem, cerebrum and cerebellum) are also metabolically similar. In cerebrum, metabolic correlations markedly weaken between adolescence and adulthood, whereas at old age, cross-region correlation patterns reflect decreased brain segregation. We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available (https://mouse.atlas.metabolomics.us/) and serves as a foundation dataset for future metabolomic studies.
Background: Exposure to air pollution increases cardiovascular morbidity and mortality. Preventing chronic cardiovascular diseases caused by air pollution relies on detecting the early effects of pollutants on the risk of cardiovascular disease development, which is limited by the lack of sensitive biomarkers. We have previously identified promising biomarkers in experimental animals but comparable evidence in humans is lacking. Methods: Air pollution is substantially worse in Beijing than in Los Angeles. We collected urine and blood samples from 26 nonsmoking, healthy adult residents of Los Angeles (mean age, 23.8 years; 14 women) before, during, and after spending 10 weeks in Beijing during the summers of 2014 and 2015. We assessed a panel of circulating biomarkers indicative of lipid peroxidation and inflammation. Personal exposure to polycyclic aromatic hydrocarbons (PAHs), a group of combustion-originated air pollutants, was assessed by urinary PAH metabolite levels. Results: Urinary concentrations of 4 PAH metabolites were 176% (95% CI, 103% to 276%) to 800% (95% CI, 509% to 1780%) greater in Beijing than in Los Angeles. Concentrations of 6 lipid peroxidation biomarkers were also increased in Beijing, among which 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid levels reached statistical significance (false discovery rate <5%), but not 8-isoprostane (20.8%; 95% CI, −5.0% to 53.6%). The antioxidative activities of paraoxonase (−9.8%; 95% CI, −14.0% to −5.3%) and arylesterase (−14.5%; 95% CI, −22.3% to −5.8%) were lower and proinflammatory C-reactive protein (101%; 95% CI, 3.3% to 291%) and fibrinogen (48.3%; 95% CI, 4.9% to 110%) concentrations were higher in Beijing. Changes in all these biomarkers were reversed, at least partially, after study participants returned to Los Angeles. Changes in most outcomes were associated with urinary PAH metabolites ( P <0.05). Conclusions: Traveling from a less-polluted to a more-polluted city induces systemic pro-oxidative and proinflammatory effects. Changes in the levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid as well as paraoxonase and arylesterase activities in the blood, in association with exposures to PAH metabolites, might have important implications in preventive medicine as indicators of increased cardiovascular risk caused by air pollution exposure.
The memory effect and retention characteristics of a Ge nanocrystal (NC) floating gate memory structure consisting of Hf-aluminate (HfAlO) tunnelling and control oxides have been investigated by means of high-frequency capacitance–voltage (C–V) and capacitance–time (C–t) measurements. The trilayer structure (HfAlO/Ge-NC/HfAlO) on Si was fabricated by pulsed-laser deposition at a relatively low temperature. A high-resolution transmission electron microscopy study revealed that the Ge nanocrystals are about 5 nm in diameter and are well distributed within the amorphous HfAlO matrix. The memory effect was revealed by the counter-clockwise hysteresis loop in the C–V curves and a high storage charge density of about 1 × 1013 cm−2 and a large flat-band voltage shift of 3.6 V have been achieved. An 8% decay in capacitance after 104 s in the C–t measurement suggests a promising retention property of Ge NC charge storage. The effects of size/density of the Ge NC, the tunnelling and control oxide layer thicknesses and their growth oxygen partial pressure to the charge storage and charge retention characteristics have been studied.
A nonvolatile flash memory device has been fabricated using carbon nanotubes ͑CNTs͒ as a floating gate embedded in HfAlO ͑the atomic ratio of Hf/ Al is 1:2͒ high-k tunneling/control oxides and its memory effect has been observed. Capacitance-voltage ͑C-V͒ measurements illustrated a 400 mV memory window during the double C-V sweep from 3 to −3 V performed at room temperature and 1 MHz. Further studies on their programming characteristics revealed that electron is difficult to be written into the CNTs and the memory effect of the structures is mainly due to the holes traps. The memory window width can remain nearly unchanged even after 10 4 s stressing, indicating excellent long term charge retention characteristics. We therefore suggest that the CNTs embedded in HfAlO can be potentially applied to floating gate flash memory devices. © 2006 American Institute of Physics. ͓DOI: 10.1063/1.2179374͔Since their discovery in the early 1990s, 1 carbon nanotubes ͑CNTs͒ have attracted much attention, both of scientific and technological interest, for possible nanoelectronic applications. To date, a number of nanoelectronic devices have been realized with CNTs, such as field effect transistors, 2-4 room-temperature single-electron transistors, 5 logic gate circuits, 6 inverters, 7 and electromechanical switches. 8 Very recently, the prototypes of memory devices based on CNT field effect transistors were also reported, 9-12 demonstrating another significant extension of CNTs applications. From then on, several groups have carried out research on the CNT-based memories. [13][14][15][16][17] In these research works, the CNTs were synthesized on a conductive Si substrate capped by several hundred nanometers of SiO 2 . Metal electrodes were evaporated on the CNTs to form source and drain electrical contact to them. The conductive Si substrate actually acts as the gate of the memory device. The function of the CNTs was the current channel, and the memory effect of the devices was attributed to the charges injected from the CNTs to the defects or charge traps in the dielectrics or the interface between the CNTs and the oxides. 15-17 The CNTs were not used as the charge storage nodes.For commonly studied flash memory devices, Si, 18 Ge, 19 and Si 1−x Ge x ͑Ref. 20͒ nanocrystals are widely used as the charge storage nodes and the memory structures are sandwiched with nanocrystals embedded in the SiO 2 or high-k dielectrics. But up to now, there is no report on flash memory devices using CNTs as a floating gate. In terms of electrical properties, CNTs have many unique advantages for the application in memory devices such as tunable band gap, high thermal stability and chemical inertness, perfect sidewall structure, and nearly zero surface states. 21,22 These unique properties are very favorable for their application as the charge storage nodes in the memory devices. In this letter, we report the fabrication of the HfAlO/ CNTs/ HfAlO/ Si memory structures and characterization of the unique memory characteristics of CNTs using as the c...
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