Tunable distributed sensing performance in Ca-based nanoparticle-doped optical fibers

Rayleigh scattering enhanced nanoparticle-doped optical fibers is a technology very promising for distributed sensing applications, however, it remains largely unexplored. This work demonstrates for the first time the possibility of tuning Rayleigh scattering and optical losses in Ca-based nanoparticle-doped silica optical fibers by controlling the kinetics of the re-nucleation process that nanoparticles undergo during fiber drawing by controlling preform feed, drawing speed and temperature. A 3D study by SEM, FIB-SEM and optical backscatter reflectometry (OBR) reveals an early-time kinetics at 1870 °C, with tunable Rayleigh scattering enhancement 43.2–47.4 dB, regarding a long-haul single mode fiber, SMF-28, and associated sensing lengths of 3–5.5 m. At 2065 °C, kinetics is slower and nanoparticle dissolution is favored. Consequently, enhanced scattering values of 24.9–26.9 dB/m and sensing lengths of 135–250 m are attained. Finally, thermal stability above 500 °C and tunable distributed temperature sensitivity are proved, from 18.6 pm/°C to 23.9 pm/°C, ∼1.9–2.4 times larger than in a SMF-28. These results show the promising future of Rayleigh scattering enhanced nanoparticle-doped optical fibers for distributed sensing

Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors

Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7asinhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116. The effects were allele specific; a CDK7asmutation conferred both sensitivity to bulky adenine analogs and resistance to covalent inhibitors. Non-transformed colon epithelial cells were resistant to these combinations, as were cancer-derived cells with p53-inactivating mutations. Apoptosis was dependent on death receptor DR5, a p53 transcriptional target whose expression was refractory to Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to sensitize cancer cells to Cdk7 inhibition. Kalan et al. find that activation of the p53 tumor suppressor protein in human colon cancer-derived cells can induce transcriptional dependency on Cdk7, analogous to constitutive dependencies described in other tumors driven by oncogenic transcription factors. This work provides a proof of concept for combining p53-activating agents with Cdk7 inhibitors to elicit synthetic lethality. Keywords: Cdk7; p53; colon cancer; synthetic lethality; transcription; 5-fluorouracil; nutlin-3; apoptosis; chemical genetics; CDK inhibitorNational Institutes of Health (U.S.) (Grant HG002668