This paper describes the design and construction of the MicroBooNE liquid argon time projection chamber and associated systems. MicroBooNE is the first phase of the Short Baseline Neutrino program, located at Fermilab, and will utilize the capabilities of liquid argon detectors to examine a rich assortment of physics topics. In this document details of design specifications, assembly procedures, and acceptance tests are reported.
Extending the productive lifespan of human cells could have major implications for diseases of aging, such as atherosclerosis. We identified a relationship between aging of human vascular smooth muscle cells (SMCs) and nicotinamide phosphoribosyltransferase (Nampt/PBEF/Visfatin), the rate-limiting enzyme for NAD ؉ salvage from nicotinamide. Replicative senescence of SMCs was preceded by a marked decline in the expression and activity of Nampt. Furthermore, reducing Nampt activity with the antagonist FK866 induced premature senescence in SMCs, assessed by serial quantification of the proportion of cells with senescence-associated -galactosidase activity. In contrast, introducing the Nampt gene into aging human SMCs delayed senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress. Nampt-mediated SMC lifespan extension was associated with increased activity of the NAD ؉ -dependent longevity enzyme SIRT1 and was abrogated in Nampt-overexpressing cells transduced with a dominant-negative form of SIRT1 (H363Y). Nampt overexpression also reduced the fraction of p53 that was acetylated on lysine 382, a target of SIRT1, suppressed an age-related increase in p53 expression, and increased the rate of p53 degradation. Moreover, add-back of p53 with recombinant adenovirus blocked the anti-aging effects of Nampt. These data indicate that Nampt is a longevity protein that can add stress-resistant life to human SMCs by optimizing SIRT1-mediated p53 degradation.Age is the greatest risk factor for myocardial infarctions and strokes (1). This risk is partly attributable to an age-related decline in the ability of vascular cells to resist stress and effectively remodel the arterial wall. Vascular smooth muscle cells (SMCs) 3 are especially important in this regard; the efficiency with which SMCs stabilize a developing atherosclerotic lesion determines whether the lesion will rupture, a potentially fatal event. Strategies to prevent the premature senescence of SMCs could be a promising approach for reducing vascular disease if molecular targets can be identified.Nicotinamide phosphoribosyltransferase (Nampt, also known as Pre-B-cell colony-enhancing factor and Visfatin (2)) is the rate-limiting enzyme for NAD ϩ biosynthesis from nicotinamide. The intracellular levels of NAD ϩ and nicotinamide have recently been identified as important for certain cell survival reactions, including those linked to the sirtuin family of protein deacetylases (3, 4). Sirtuins, such as Sir2 and its mammalian homolog SIRT1, consume NAD ϩ and generate nicotinamide as they hydrolytically remove a targeted acetyl group (3). Nicotinamide is a known inhibitor of NAD ϩ -dependent deacetylation reactions. Therefore, pathways that both replenish NAD ϩ and clear nicotinamide could be vital to SIRT1 activity.Recently, we discovered that Nampt was substantially upregulated when a uniquely long-lived human vascular SMC line was subjected to the stress of complete serum withdrawal (5). Here, we report that Nampt i...
Sm (25). We prepared spectroscopic alpha sources (20-100 μg) from the three activations and counted them during several months using a silicon surface-barrier detector at Kanazawa University (Fig. 1, 25 Galactic-disk enrichment in low-metallicity gas (Fig. 3). This reduces the age of late events (≥ 50 Ma) (age is measured in this work relative to the birth of the solar system) but has a minor effect on earlier events (Table 1). Samarium-146 observations in terrestrial samples can be divided into two groups: (i) most terrestrial rocks display a 142 Nd/ 144 Nd ratio higher by ~18 parts per million (ppm) than CHUR (9) and (ii) anomalies in the 142 Nd/ 144 Nd ratio relative to the terrestrial standard, both positive, in rocks from Greenland and Australia (2,10), and negative, in rocks from Northern Quebec (2,11).
Mixture A, % Mixture 8. % RESULTSRecently we showed that sulfonation of n-toluenesulfonic acid in fuming sulfuric acid leads to the formation of 2,5-, 3,4-, and 3,5-toluenedisulfonic acid (11). It was there-(22) H. This paper describes a compact inductively coupledtype of source has been eliminated, and pneumatic nebuplasma-optical emission system for the trace determinalization is employed in place of the more elaborate ultration of metallic elements in solution. Theoretical consid-sonic method. Some characteristics of the plasma are erations are presented to determine operating parameters reported. Detection limits are in the range 0.1 -1 0 ng/ml which agree well with the empirically determined values.for most elements studied. The present facility is readily The aerosol desolvation system commonly used with this adaptable to simultaneous multielement trace analysis.
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