Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. However, it is unknown if mTOR inhibition affects aging or its consequences in humans. To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly.

Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.

Gaofen-3 (GF-3), the first Chinese spaceborne synthetic aperture radar (SAR) in C-band for civil applications, was launched on August 2016. Some studies have examined the use of GF-3 SAR data for ocean and coastal observations, but these studies generally focus on one particular application. As GF-3 has been in operation over two years, it is essential to evaluate its performance in ocean observation, a primary goal of the GF-3 launch. In this paper, we offer an overview demonstrating the capabilities of GF-3 SAR in ocean and coastal observations by presenting several representative cases, i.e., the monitoring of intertidal flats, offshore tidal turbulent wakes and oceanic internal waves, to highlight the GF-3's full polarimetry, high spatial resolution and wide-swath imaging advantages. Moreover, we also present a detailed analysis of the use of GF-3 quad-polarization data for sea surface wind retrievals and wave mode data for sea surface wave retrievals. The case studies and statistical analysis suggest that GF-3 has good ocean and coastal monitoring capabilities, though further improvements are possible, particularly in radiometric calibration and stable image quality.kilometers. Wide-swath or ScanSAR images generally have a spatial resolution of tens of meters and, more importantly, can map a large area of the open sea and coast, which makes them particularly suitable for studying meso-scale oceanic and atmospheric processes, e.g., by mapping the distribution of internal ocean waves [2], observing atmospheric solitons [3], estimating the wind speed of tropical cyclones [4], and measuring sea surface velocity [5].The year 2007 marks an important advance in the development of spaceborne SAR; two X-band spaceborne SAR, the TerraSAR-X (TSX) and Cosmo-SkyMed and the C-band SAR, Radarsat-2 (R2), were launched. Compared with previous spaceborne SAR missions, the new generation of SAR sensors has several advantages. One advantage is that the new generation can acquire images with a high spatial resolution of up to 1 m in spotlight mode [6][7][8]. This offers a unique opportunity to detect targets in the ocean and coast, e.g., for ship detection [9][10][11]. The other advantage is that these SAR sensors have polarimetric capabilities of acquiring data in different polarization combinations of VV, HH, VH and HV. These SAR polarimetric data are widely exploited for oil spill detection or classification [12][13][14], analysis of objects scattering or their classification in coastal intertidal flats [15][16][17], and sea ice detection and classification [18][19][20]. In addition to the general advantages of the aforementioned high spatial resolution and polarimetry, advanced SARs have constellation configuration design. The Cosmo-SkyMed, TSX/TanDEM-X (TDX) and Sentinel-1A/1B missions, as well as the forthcoming Radarsat Constellation Mission (RCM), all operate in constellations, which significantly reduces the temporal intervals of SAR data acquisition and therefore enhances the capture of dynamic sea surface information ...

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