Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations.

BACKGROUND: Previous studies have indicated that tumor mitochondrial DNA (mtDNA) mutations are primarily shaped by relaxed negative selection, which is contradictory to the critical roles of mtDNA mutations in tumorigenesis. Therefore, we hypothesized that site-specific selection may influence tumor mtDNA mutations. METHODS: To test our hypothesis, we developed the largest collection of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA mutation patterns. RESULTS: Our data demonstrated that both positive and negative selections acted on specific positions or functional units of tumor mtDNAs, although the landscape of these mutations was consistent with the relaxation of negative selection. In particular, mutation rate (mutation number in a region/region bp length) in complex V and tRNA coding regions, especially in ATP8 within complex V and in loop and variable regions within tRNA, were significantly lower than those in other regions. While the mutation rate of most codons and amino acids were consistent with the expectation under neutrality, several codons and amino acids had significantly different rates. Moreover, the mutations under selection were enriched for changes that are predicted to be deleterious, further supporting the evolutionary constraints on these regions. CONCLUSION: These results indicate the existence of site-specific selection and imply the important role of the mtDNA mutations at some specific sites in tumor development

A low phase noise high power Er-fiber frequency comb synchronized to the hydrogen maser clock by harmonic phase locking

We demonstrate a low phase noise all polarization-maintaining (PM) Er-fiber optical frequency comb (OFC) with low phase noise, which is synchronized to the hydrogen maser clock (HMC) using the 18th harmonic of the repetition rate for tight phase locking. The instability of the locked carrier envelope offset frequency is 1.24 × 10−18@1 s, the phase noise of the OFC is −96 dBc/Hz at 1 Hz offset, and the corresponding RMS timing jitter of the repetition rate is 62 fs (1 Hz–1 MHz). The residual frequency instability of the repetition rate (200 MHz) is 1.46 × 10−14@1 s, and the residual phase noise of the OFC normalized to 10 MHz is −138 dBc/Hz at 1 Hz offset and declines to about −160 dBc/Hz at the far-end, much lower than that of the HMC (−122 dBc/Hz at 1 Hz and −156 dBc/Hz at the far-end)

Polarization-multiplexed dual-comb fiber laser based on an all-polarization-maintaining cavity configuration

In this study, we present a polarization-multiplexed, erbium-doped dual-comb fiber laser based on an all-polarization-maintaining cavity configuration. We observed that the dual-comb fiber laser easily realized the self-starting mode-locking operation due to the non-linear amplifying loop mirror (NALM) with a non-reciprocal phase shifter. Furthermore, owing to the sharing of the NALM part, the two outputs from this laser configuration had similar center wavelengths, with small different repetition rates (∆frep). In the free-running operation, the standard deviation of relative stability for Δfrep of 2.09 kHz was measured to be 1.59 Hz, and the full width at half-maximum of the relative beat note between the two frequency combs in the optical frequency domain was approximately 1 kHz. These results show that the two frequency combs from this laser configuration have high relative stability and mutual coherence

Runoff and Sediment Response to Cascade Hydropower Exploitation in the Middle and Lower Han River, China

With the rapid development of hydropower exploitation in China, changes in runoff and sediment transport have become a significant issue that cannot be neglected. In this study, the Han River was selected as a study case, where the runoff variation and changes in sediment load at the Baihe, Huangjiagang, Huangzhuang, and Xiantao stations were analyzed in different time periods. The results indicate that impact of cascade hydropower exploitation on runoff and sediment transport is significantly different even during the same time periods. After reservoir regulation, the decreasing of sediment load is faster than that of runoff. Strong positive correlation between runoff and sediment load exists during different time periods, while reservoir operation leads to different turning points at the Baihe, Huangjiagang, Huangzhuang, and Xiantao stations in the middle and lower Han River. As a key driving factor, runoff variation contributed to sediment transport with different impact index CR. The impact index CR before and after the first change point at the Baihe, Huangjiagang, Huangzhuang, and Xiantao stations is 43.35%, −3.68%, 11.17%, and 30.12%, respectively. This study helps us understand and evaluate the hydrological changes under cascade hydropower exploitation in the middle and lower Han River