Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD + -dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC1a isolated from cells, and (iii) although SIRT1 deacetylates PGC-1a in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1. Key words: Fluor de Lys, resveratrol, SIRT1Abbreviations: AMPK, AMP-activated protein kinase; HPLC, high performance liquid chromatography; NAM, nicotinamide; PGC-1a, peroxisome proliferator-activated receptor-c coactivator-1a; Sir2, silence information regulator 2; SIRTs, sirtuins. Sirtuins constitute the unique family of NAD + -dependent protein deacetylases. Silent information regulator 2 (Sir2) is a sirtuin in budding yeast Saccharomyces cerevisiae and its activity mediates lifespan extension induced by calorie restriction (1). The mammalian Sir2 ortholog, SIRT1, is also induced by calorie restriction and promotes cell survival (2), triggers lipolysis and loss of fat (3), and controls glucose homeostasis (4). The biological effects of SIRT1 are mediated by its ability to deacetylate several important transcriptional factors such as Peroxisome proliferator-activated receptor-c coactivator 1alpha (PGC-1a), p53, and FOXO proteins and consequently regulate their activities (5). PGC-1a, which is activated upon deacetylation by SIRT1, plays an important role in the regulation of mitochondrial function and fatty acid oxidation (4). In contrast, p53 is inactivated once deacetylated by SIRT1 (5), suggesting that SIRT1 may protect cells from apoptosis under conditions of nutrient restriction. Taken together, these findings demonstrate that SIRT1 activity stimulates energy metabolism, improves mitochondrial function and promotes cell survival. Therefore, pharmacological activation of SIRT1 in vivo may provide a new avenue to maintain metabolic homeostasis.Molecular screening of SIRT1 activators led to the identification of plant polyphenols as SIRT1 activators, among which is resveratrol (6). The notion that resveratrol is a SIRT1 activator is consistent with two later pharmacological ...

We propose multi-band metamaterial absorbers at microwave frequencies. The design, the analysis, the fabrication, and the measurement of the absorbers working in multiple bands are presented. The numerical simulations and the experiments in the microwave anechoic chamber were performed. The metamaterial absorbers consist of an delicate arrangement of donut-shape resonators with different sizes and a metallic background plane, separated by a dielectric. The near-perfect absorptions of dual, triple and quad peaks are persistent with polarization independence, and the effect of angle of incidence for both TE and TM modes was also elucidated. It was also found that the multiple-reflection theory was not suitable for explaining the absorption mechanism of our investigated structures. The results of this study are promising for the practical applications.

Perfect metamaterial absorber (PMA) can intercept electromagnetic wave harmful for body in Wi-Fi, cell phones and home appliances that we are daily using and provide stealth function that military fighter, tank and warship can avoid radar detection. We reported new concept of water droplet-based PMA absorbing perfectly electromagnetic wave with water, an eco-friendly material which is very plentiful on the earth. If arranging water droplets with particular height and diameter on material surface through the wettability of material surface, meta-properties absorbing electromagnetic wave perfectly in GHz wide-band were shown. It was possible to control absorption ratio and absorption wavelength band of electromagnetic wave according to the shape of water droplet–height and diameter– and apply to various flexible and/or transparent substrates such as plastic, glass and paper. In addition, this research examined how electromagnetic wave can be well absorbed in water droplets with low electrical conductivity unlike metal-based metamaterials inquiring highly electrical conductivity. Those results are judged to lead broad applications to variously civilian and military products in the future by providing perfect absorber of broadband in all products including transparent and bendable materials.

The efficacy of therapeutic antibodies that induce antibody-dependent cellular cytotoxicity can be improved by reduced fucosylation. Consequently, fucosylation is a critical product attribute of monoclonal antibodies produced as protein therapeutics. Small molecule fucosylation inhibitors have also shown promise as potential therapeutics in animal models of tumors, arthritis, and sickle cell disease. Potent small molecule metabolic inhibitors of cellular protein fucosylation, 6,6,6-trifluorofucose per-O-acetate and 6,6,6-trifluorofucose (fucostatin I), were identified that reduces the fucosylation of recombinantly expressed antibodies in cell culture in a concentration-dependent fashion enabling the controlled modulation of protein fucosylation levels. 6,6,6-Trifluorofucose binds at an allosteric site of GDP-mannose 4,6-dehydratase (GMD) as revealed for the first time by the X-ray cocrystal structure of a bound allosteric GMD inhibitor. 6,6,6-Trifluorofucose was found to be incorporated in place of fucose at low levels (<1%) in the glycans of recombinantly expressed antibodies. A fucose-1-phosphonate analog, fucostatin II, was designed that inhibits fucosylation with no incorporation into antibody glycans, allowing the production of afucosylated antibodies in which the incorporation of non-native sugar is completely absent-a key advantage in the production of therapeutic antibodies, especially biosimilar antibodies. Inhibitor structure-activity relationships, identification of cellular and inhibitor metabolites in inhibitor-treated cells, fucose competition studies, and the production of recombinant antibodies with varying levels of fucosylation are described.

We propose polarization-independent and dual-broadband metamaterial absorbers at microwave frequencies. This is a periodic meta-atom array consisting of metal-dielectric-multilayer truncated cones. We demonstrate not only one broadband absorption from the fundamental magnetic resonances but additional broadband absorption in high-frequency range using the third-harmonic resonance, by both simulation and experiment. In simulation, the absorption was over 90% in 3.93-6.05 GHz, and 11.64-14.55 GHz. The corresponding experimental absorption bands over 90% were 3.88-6.08 GHz, 9.95-10.46 GHz and 11.86-13.84 GHz, respectively. The origin of absorption bands was elucidated. Furthermore, it is independent of polarization angle owing to the multilayered circular structures. The design is scalable to smaller size for the infrared and the visible ranges.