RESUMO
Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.
Assuntos
Endodesoxirribonucleases , Neoplasias , Peptídeos , Poli ADP Ribosilação , RNA Longo não Codificante , Reparo do DNA , Endodesoxirribonucleases/metabolismo , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Peptídeos/farmacologia , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
We performed experiments involving the fabrication of Mo/Si multilayer coatings and established a model of the deposition process. The surface and interface roughness, surface power spectral density, layer structures, and coating reflectivity were characterized for different substrate inclination angles. The surface and interface roughness increase and the coating reflectivity decreases with an increase in the substrate inclination angle, especially for large angles (50-70°). The model was applied to explain this phenomenon, and a proposal to reduce the interfacial roughness caused by substrate inclination angles is presented.
RESUMO
High-quality coatings of fluoride materials are in extraordinary demand for use in deep ultraviolet (DUV) lithography. Gadolinium fluoride (GdF3) thin films were prepared by a thermal boat evaporation process at different substrate temperatures. GdF3 thin film was set at quarter-wave thickness (â¼27 nm) with regard to their common use in DUV/vacuum ultraviolet optical stacks; these thin films may significantly differ in nanostructural properties at corresponding depositing temperatures, which would crucially influence the performance of the multilayers. The measurement and analysis of optical, structural, and mechanical properties of GdF3 thin films have been performed in a comprehensive characterization cycle. It was found that depositing GdF3 thin films at relative higher temperature would form a rather dense, smooth, homogeneous structure within this film thickness scale.
RESUMO
In this Letter, we study diffuse reflectance and photoluminescence spectra for O(2-) fully coordinated green-emitting Ce(3+) and N(3-) partially coordinated red Ce(3+) in Ca(3)Sc(2)Si(3)O(12)(CSS):Ce(3+), N(3-) as a function of CeO(2) and Si(3)N(4) contents in the raw material. Our results indicate that the presence of N(3-) can enhance Ce(3+) solubility in the form of red centers in CSS. At low Ce(3+) concentration, green Ce(3+) forms preferentially while red Ce(3+) hardly forms even if N(3-) content in the raw material is sufficient. There exists a threshold concentration of green Ce(3+); only beyond that can color tunable luminescence with enriched red emission be achieved. Energy transfer from green Ce(3+) to red Ce(3+) is also studied, as only the green Ce(3+) is excited by blue light.
RESUMO
Most of the optical axes in modern systems are bent for optomechanical considerations. Antireflection (AR) coatings for polarized light at oblique incidence are widely used in optical surfaces like prisms or multiform lenses to suppress undesirable reflections. The optimal design and fabrication method for AR coatings with large-angle range (68°-74°) for a P-polarized 193 nm laser beam is discussed in detail. Experimental results showed that after coating, the reflection loss of a P-polarized laser beam at large angles of incidence on the optical surfaces is reduced dramatically, which could greatly improve the output efficiency of the optical components in the deep ultraviolet vacuum range.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Terapia a Laser/métodos , Absorção , Desenho de Equipamento , Lasers , Luz , Dispositivos Ópticos , Óptica e Fotônica , Refratometria/instrumentação , Reprodutibilidade dos TestesRESUMO
We propose a method to maintain the symmetry condition of the refractive index with respect to a dielectric buffer layer for a long-range surface plasmon resonance (LRSPR) configuration. The symmetry condition was maintained by changing the concentration of the ethylene glycol aqueous solution (sample buffer layer) to match the refractive index of the MgF2 film. Maintenance of the symmetry condition is necessary for exciting the LRSPR mode and increasing the electric field intensity near the film. We used a four-phase Kretschmann resonance setup composed of a K9 prism, MgF2 film, Ag film, and sample buffer layer. The incident angle-dependent surface-enhanced Raman scattering (SERS) spectra were measured in the evanescent field. At the SPR angle, the SERS signal of the symmetric configuration was 60 times higher than that of the conventional SPR configuration. Moreover, the electric field penetration depth of the symmetric long-range surface plasmon configuration (>1000 nm) was longer than that of their asymmetric counterparts. The enhancement factor of the symmetric configuration was 8.6 × 107, which corresponded to the lowest detectable concentration for 4-mercaptopyridine, reaching 1.0 × 10-10 M at the resonance angle. Thus, the symmetric LRSPR configuration has great potential for label-free sensing and detection of macromolecules and biomolecules.
RESUMO
A 2x2 digital optical switch using two symmetrical unidirectional Bragg grating couplers is proposed and studied in this paper. A low-loss polymer is used as waveguide material, and the Bragg grating coupling efficiency is optimized to be 22%, then the unidirectional coupling efficiency of 99.9% is achieved in theory. The performance of the switch based on the unidirectional couplers with Bragg gratings is theoretically modeled and simulated. Finally, the 2.4dB insertion loss, the -17dB crosstalk between two output ports, the 28 dB extinction ratio, the 1.5ms response speed and the 87mW power consumption are experimentally demonstrated with this regime.