Shifts of a resonance line in a dense atomic sample

We study the collective response of a dense atomic sample to light essentially exactly using classical-electrodynamics simulations. In a homogeneously broadened atomic sample there is no overt Lorentz-Lorenz local field shift of the resonance, nor a collective Lamb shift. However, addition of inhomogeneous broadening restores the usual mean-field phenomenology

Low molecular weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer

Low molecular weight cyclin E (LMW-E) are oncogenic forms of cyclin E that are post translationally generated by neutrophil elastase (NE) mediated cleavage of the 50 KDa full-length cyclin E1 (FL-cycE, encoded by CCNE1gene). The resultant N-terminus deleted (40 amino acids) form of LMW-E is detected in breast cancer cells and tumor tissues, but not in normal mammary epithelial cells or adjacent normal tissues. Unlike FL-cycE, LMW-E drives mammary epithelial cell transformation in human cells and spontaneous mammary tumor formation in transgenic mouse models, but the oncogenic mechanisms of LMW-E and its unique function(s) independent of FL-cycE are not fully understood. It is currently assumed that LMW-E drives the tumorigenic process by promoting G1/S cell cycle transition and accelerating mitotic exit. Biochemical features such as longer protein half-life, higher affinity to its kinase partner CDK2, and resistance to endogenous CDK inhibitors such as p21 and p27 all promote the tumorigenic ability of LMW-E. Clinical studies in breast cancer reveal that overexpression of LMW-E predicts recurrence and poor survival in breast cancer patients independent of molecular subtype, Ki67 status, nodal status, or tumor grade, suggesting LMW-E may be driving breast cancer development independent of its role in cell proliferation. In the current study, we tested the hypothesis that LMW-E promotes genomic instability by deregulating DNA replication and damage repair. We generated immortalized pre-cancerous human mammary epithelial cells (hMECs) engineered to express doxycycline inducible LMW-E or FL-cycE in CCNE1 knock-out background. We found that, unlike LMW-E, FL-cycE overexpression led to DNA replication stress and DNA damage accumulation, resulting in reduced cell viability. LMW-E overexpression, on the other hand, promoted cell survival under replication stress, resulting in persistent genomic instability. RNA-sequencing results showed LMW-E but not FL-cycE overexpression enhanced DNA replication and damage repair pathways. Molecularly, LMW-E but not FL-cycE strongly interacted with CDC6, bound to chromatin, and facilitated replication stress tolerance by upregulating pre-replication complex assembly. LMW-E also mediated DNA repair by upregulating the levels of RAD51 and C17orf53, showing a dominant repairing effect over DNA damage induced by FL-cycE. Moreover, targeting the replication stress response pathway ATR-CHK1-RAD51 with small molecule inhibitors significantly decreased viability of LMW-E overexpressing hMECs and breast cancer cells. Lastly, we showed that positive LMW-E status was associated with genomic instability in tumors from a cohort of 725 patients diagnosed with early-stage breast cancer, further supporting our hypothesis that LMW-E promotes genomic instability to fuel breast cancer development. Collectively, our findings delineated a novel role for LMW-E in breast tumorigenesis mediated by replication stress tolerance and genomic instability, providing novel therapeutic strategies for LMW-E overexpressing breast cancers

Three photon absorption in ZnO and ZnS crystals

We report a systematic investigation of both three-photon absorption (3PA)spectra and wavelength dispersions of Kerr-type nonlinear refraction in wide-gap semiconductors. The Z-scan measurements are recorded for both ZnO and ZnS with femtosecond laser pulses. While the wavelength dispersions of the Kerr nonlinearity are in agreement with a two-band model, the wavelength dependences of the 3PA are found to be given by (3Ephoton/Eg-1)5/2(3Ephoton/Eg)-9. We also evaluate higher-order nonlinear optical effects including the fifth-order instantaneous nonlinear refraction associated with virtual three-photon transitions, and effectively seventh-order nonlinear processes induced by three-photon-excited free charge carriers. These higher-order nonlinear effects are insignificant with laser excitation irradiances up to 40 GW/cm2. Both pump-probe measurements and three-photon figures of merits demonstrate that ZnO and ZnS should be a promising candidate for optical switching applications at telecommunication wavelengths.Comment: 13 pages, 7 figure