Abstract:We demonstrate a novel mechanism for low power optical detection and modulation in a slotted waveguide geometry filled with nonlinear electro-optic polymers. The nanoscale confinement of the optical mode, combined with its close proximity to electrical contacts, enables the direct conversion of optical energy to electrical energy, without external bias, via optical rectification, and also enhances electro-optic modulation. We demonstrate this process for power levels in the sub-milliwatt regime, as compared to the kilowatt regime in which optical nonlinear effects are typically observed at short length scales. Our results suggest that a new class of detectors based on nonlinear optics may be practical.

Although gigahertz-scale free-carrier modulators have been demonstrated in silicon, intensity modulators operating at terahertz speeds have not been reported because of silicon's weak ultrafast nonlinearity. We have demonstrated intensity modulation of light with light in a silicon-polymer waveguide device, based on the all-optical Kerr effect-the ultrafast effect used in four-wave mixing. Direct measurements of time-domain intensity modulation are made at speeds of 10 GHz. We showed experimentally that the mechanism of this modulation is ultrafast through spectral measurements, and that intensity modulation at frequencies in excess of 1 THz can be obtained. By integrating optical polymers through evanescent coupling to silicon waveguides, we greatly increase the effective nonlinearity of the waveguide, allowing operation at continuous-wave power levels compatible with telecommunication systems. These devices are a first step in the development of large-scale integrated ultrafast optical logic in silicon, and are two orders of magnitude faster than previously reported silicon devices.

Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.

BackgroundColistin acts as the last line of defense against severe infections caused by carbapenem-resistant Enterobacteriaceae. Infections caused by extensively drug-resistant isolates coproducing MCR and carbapenemases have posed a serious public health concern.PurposeIn this study, we reported the first clinical colistin and carbapenem-resistant Enterobacter hormaechei isolate SCNJ07 coharboring blaNDM-1 and mcr-9 from a patient with bloodstream infection in China.MethodsBacterial antimicrobial susceptibility testing was performed using the broth microdilution method. Conjugation assay was carried out to investigate the transferability of mcr-9 and blaNDM-1. Whole-genome sequencing of strain SCNJ07 was performed using an Illumina HiSeq system and the genetic characteristics of the mcr-9- and blaNDM-1-harboring plasmids were analyzed.ResultsConjugation assays revealed that both blaNDM-1 and mcr-9 genes could successfully transfer their resistance phenotype to Escherichia coli strain J53. Whole genome sequencing showed that SCNJ07 possessed an FIB36:FIIY4 type self-transmissible plasmid bearing blaNDM-1, which possessed high similarity to previously reported pRJF866 in China. mcr-9 was located on a ~28-kb self-transmissible plasmid pMCR-SCNJ07 with both IncHI2 and IncR replicons. Two copies of intact IS903 that bracketed a ~8-kb region containing the mcr-9 gene were identified in pMCR-SCNJ07. BLASTn analysis revealed that a number of mcr-9-positive plasmids have been around for a while among Enterobacteriaceae worldwide.ConclusionThis study reveals the likelihood of a wide dissemination of this newly identified colistin resistance gene mcr-9 among Enterobacteriaceae. Further surveillance is urgently needed to understand the prevalence and dissemination of mcr-9, thereby facilitating establishment of measures to control its spread.