No abstract

Nicotinamide N-methyltransferase (NNMT) was recently identified as one clear cell renal cell carcinoma (ccRCC)-associated gene by analyzing full-length complementary DNA-enriched libraries of ccRCC tissues. The aim of this study is to investigate the potential role of NNMT in cellular invasion. A strong NNMT expression is accompanied with a high invasive activity in ccRCC cell lines, and small interfering RNA-mediated NNMT knockdown effectively suppressed the invasive capacity of ccRCC cells, whereas NNMT overexpression markedly enhanced that of human embryonic kidney 293 (HEK293) cells. A positive correlation between the expression of NNMT and matrix metallopeptidase (MMP)-2 was found in ccRCC cell lines and clinical tissues. The treatment of blocking antibody or inhibitor specific to MMP-2 significantly suppressed NNMT-dependent cellular invasion in HEK293 cells. Furthermore, SP-1-binding region of MMP-2 promoter was found to be essential in NNMT-induced MMP-2 expression. The specific inhibitors of PI3K/Akt signaling markedly decreased the binding of SP1 to MMP-2 promoter as shown by chromatin immunoprecipitation assay. We also demonstrated that PI3K/Akt pathway plays a role in NNMT-dependent cellular invasion and MMP-2 activation. Moreover, short hairpin RNA-mediated knockdown of NNMT expression efficiently inhibited the growth and metastasis of ccRCC cells in non-obese diabetic severe combined immunodeficiency mice. Taken together, the present study suggests that NNMT has a crucial role in cellular invasion via activating PI3K/Akt/SP1/MMP-2 pathway in ccRCC.

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Typhoon Morakot struck Taiwan during 6-9 August 2009, and it produced the highest rainfall (approaching 3000 mm) and caused the worst damage in the past 50 yr. Typhoon-monsoon flow interactions with mesoscale convection, the water vapor supply by the monsoon flow, and the slow moving speed of the storm are the main reasons for the record-breaking precipitation. Analysis of the typhoon track reveals that the steering flow, although indeed slow, still exceeded the typhoon moving speed by approximately 5 km h~'(l km h~' = 0.28 m s~') during the postlandfall period on 8 August, when the rainfall was the heaviest. The CloudResolving Storm Simulator (CReSS) is used to study the dynamics of the slow storm motion toward the northnorthwest upon leaving Taiwan. The control simulations with 3-km grid size compare favorably with the observations, including the track, slow speed, asymmetric precipitation pattern, mesoscale convection, and rainfall distribution over Taiwan. Sensitivity tests with reduced moisture content reveal that not only did the model rainfall decrease but also the typhoon translation speed increased. Specifically, the simulations consistently show a discernible impact on storm motion by as much as 50%, as the storms with full moisture move slower(~5 km h~'). while those with limited moisture (s25%) move faster (-10 km h"'). Thus, in addition to a weak steering flow, the prolonged asymmetric precipitation in Typhoon Morakot also contributed to its very slow motion upon leaving Taiwan, and both lengthened the heavy-rainfall period and increased the total rainfall amount. The implications of a realistic representation of cloud microphysics from the standpoint of tropical cyclone track forecasts are also briefly discussed.

The present study investigates the characteristics of low-level jets (LLJs) (≥12.5 m s−1) below 600 hPa over northern Taiwan in the mei-yu season and their relationship to heavy rainfall events (≥50 mm in 24 h) through the use of 12-h sounding data, weather maps at 850 and 700 hPa, and hourly rainfall data at six surface stations during the period of May–June 1985–94. All LLJs are classified based on their height, appearance (single jet or double jet), and movement (migratory and nonmigratory). The frequency, vertical structure, and spatial and temporal distribution of LLJs relative to the onset of heavy precipitation are discussed. Results on the general characteristics of LLJs suggest that they occurred about 15% of the time in northern Taiwan, with a top speed below 40 m s−1. The level of maximum wind appeared mostly between 850 and 700 hPa, with highest frequency at 825–850 hPa. A single jet was observed more often (76%) than a double jet (24%), while in the latter case a barrier jet usually existed at 900–925 hPa as the lower branch. Migratory and nonmigratory LLJs each constituted about half of all cases, and there existed no apparent relationship between their appearance and movement. Migratory LLJs tended to be larger in size, stronger over a thicker layer, more persistent, and were much more closely linked to heavy rainfall than nonmigratory jets. They often formed over southern China between 20° and 30°N and moved toward Taiwan presumably along with the mei-yu frontal system. Before and near the onset of the more severe heavy rain events (≥100 mm in 24 h) in northern Taiwan, there was a 94% chance that an LLJ would be present over an adjacent region at 850 hPa, and 88% at 700 hPa, in agreement with earlier studies. Occurrence frequencies of LLJs for less severe events (50–100 mm in 24 h) were considerably lower, and the difference in accumulative rainfall amount was seemingly also affected by the morphology of the LLJs, including their strength, depth, elevation of maximum wind, persistence, proximity to northern Taiwan, source region of moisture, and their relative timing of arrival before rainfall. During the data period, about 40% of all migratory LLJs at 850 or 700 hPa passing over northern Taiwan were associated with heavy rainfall within the next 24 h. The figure, however, was much lower compared to earlier studies, and some possible reasons are offered to account for this deficit.