Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Evolution of collaboration and optimization of impact: self-organization in multinational research

Scientometrics - The expanding presence of multinational research teams highlights the importance of characterizing the outcomes of international collaboration. Herein, we characterize the...     

A low-phase-noise K-band CMOS VCO

A novel circuit topology for low-phase-noise voltage controlled oscillators (VCOs) is presented in this letter. By employing a PMOS cross-coupled pair with a capacitive feedback, superior circuit performance can be achieved especially at higher frequencies. Based on the proposed architecture, a prototype VCO implemented in a 0.18-/spl mu/m CMOS process is demonstrated for K-band applications. From the measurement results, the VCO exhibits a 510-MHz frequency tuning range at 20GHz. The output power and the phase noise at 1-MHz offset are -3dBm and -111dBc/Hz, respectively. The fabricated circuit consumes a dc power of 32mW from a 1.8-V supply voltage.     

Artificial neural networks and statistical modeling for electronic stress prediction using thermal profiling

Electronic components are constantly under stress due to factors such as signal density, temperature, humidity, and high current and voltage. Relatively little research has emphasized stress-level prediction under voltage stress. The purpose of this paper was to develop an electronic thermal profile model for stress-level prediction utilizing neural network (NN) and statistical approaches, such as multivariate regression models. Electronic components were removed from boards, subjected to different levels of stress, then replaced. An infrared camera was then used to capture information about component temperature changes over time under normal operating and stress conditions. Statistical analysis of the captured images suggests a strong correlation between thermal profiles and voltage stress levels. Artificial neural network (ANN) and statistical approaches were used to model temperature change profiles for components that had been stressed at different levels, and their predictive ability was compared. Separate data sets were used for model development and model verification. ANN prediction rates were around 70%, compared to 30% for the statistical approach. Experiments were also conducted to evaluate the robustness of the ANN model to the presence of noise in the data. Results suggested that the ANN model was able to accommodate the presence of noise. Various backpropagation (BP) learning algorithms were also evaluated and yielded similar average error rates. A 3-2-1 ANN topology performed better than 3-3-1 or 3-2-2-1 topologies, perhaps because the 3-2-1 topology has a higher data sample to nodes ratio than the other topologies.     

Fabrication of 1.55 μm VCSELs on Si using metallic bonding

Using AuGeNiCr multilayered metals as the wafer bonding medium, long-wavelength GaInAsP/InP vertical cavity surface emitting lasers employing Al-oxide/Si as the upper and lower distributed Bragg reflectors were fabricated on Si substrate with the bonding interface formed outside the vertical cavity surface emitting laser cavity. Laser emission at 1.545 μm was measured under pulsed operations near room temperature. The low-temperature metallic bonding process demonstrates a great potential in device fabrication     

Highly Efficient Orange and Green Solid‐State Light‐Emitting Electrochemical Cells Based on Cationic IrIII Complexes with Enhanced Steric Hindrance

Highly efficient orange and green emission from single‐layered solid‐state light‐emitting electrochemical cells based on cationic transition‐metal complexes [Ir(ppy)₂sb]PF₆ and [Ir(dFppy)₂sb]PF₆ (where ppy is 2‐phenylpyridine, dFppy is 2‐(2,4‐difluorophenyl)pyridine, and sb is 4,5‐diaza‐9,9′‐spirobifluorene) is reported. Photoluminescence measurements show highly retained quantum yields for [Ir(ppy)₂sb]PF₆ and [Ir(dFppy)₂ sb]PF₆ in neat films (compared with quantum yields of these complexes dispersed in m‐bis(N‐carbazolyl)benzene films). The spiroconfigured sb ligands effectively enhance the steric hindrance of the complexes and reduce the self‐quenching effect. The devices that use single‐layered neat films of [Ir(ppy)₂sb]PF₆ and [Ir(dFppy)₂sb]PF₆ achieve high peak external quantum efficiencies and power efficiencies of 7.1 % and 22.6 lm W^–1) at 2.5 V, and 7.1 % and 26.2 lm W^–1 at 2.8 V, respectively. These efficiencies are among the highest reported for solid‐state light‐emitting electrochemical cells, and indicate that cationic transition‐metal complexes containing ligands with good steric hindrance are excellent candidates for highly efficient solid‐state electrochemical cells.