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.     

Sintering behaviour of fluorapatite–silicate composites produced from natural fluorapatite and quartz

In this work, the sintering behaviour of fluorapatite (FAp)–silicate composites prepared by mixing variable amounts of natural quartz (2.5 wt% to 20 wt%) and FAp was studied. The composites were pressureless sintered in air at temperatures from 1000 °C to 1350 °C. The effects of temperatures on the densification, phase formation, chemical bonding and Vickers hardness of the composites were evaluated. All the samples exhibited mixed phase, comprising FAp and francolite as the major constituents along with some minor phases of cristobalite, wollastonite, dicalcium silicate and/or whitlockite dependent on the quartz content and sintering temperature. The composite containing 2.5 wt% quartz exhibited the best sintering properties. The highest bulk density of 3 g/cm³ and a Vickers hardness of >4.2 GPa were obtained for the 2.5 wt% quartz–FAp composite when sintered at 1100 °C. The addition of quartz was found to alter the microstructure of the composites, where it exhibited a rod-like morphology when sintered at 1000 °C and a regular rounded grain structure when sintered at 1350 °C. A wetted grain surface was observed for composites containing high quartz content and was believed to be associated with a transient liquid phase sintering.     

Mixed-Metal MOF-74 Templated Catalysts for Efficient Carbon Dioxide Capture and Methanation

The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni²⁺ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg²⁺ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO₂ adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO₂ methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg²⁺-containing MOF framework, the composite system retains a portion of its CO₂ adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO₂ utilization.     

Control of reactive distillation production of high-purity isopropanol

The process characteristics and control strategy of a high-purity IPA reactive distillation column were investigated. A robust nominal operation was found by maintaining an excess of propylene feed to the column and recycling the unreacted propylene to the feed instead of the top stage. Stage temperature and propylene composition with one-to-one relationship with reboiler duty and propylene feed are selected as controlled variables for maintaining bottom purity and feed ratio in the presence of possible measurement bias respectively. High nonlinearity between selected input–output pair was reduced by using variable transformation. Dynamic simulations demonstrated that such a control scheme with nonlinear transformed variable was capable of providing much superior control performance than the one using natural variable.     

The method of double averaging: an approach for modeling power-factor-correction switching converters

This paper describes the modeling of power-factor-correction converters under average-current-mode control, which are widely used in switch-mode power supply applications. The objective is to identify stability boundaries in terms of major circuit parameters for facilitating design of such converters. The approach employs a double averaging procedure, which first applies the usual averaging over the switching period and subsequently applies generalized averaging over the mains period. The resulting model, after two averaging steps and application of a harmonic balance procedure, is nonlinear and capable of describing the low-frequency nonlinear dynamics of the system. The parameter ranges within which stable operation is guaranteed can be accurately and easily found using this model. Experimental measurements are provided for verification of the analytical results.     

High dynamic range InP HBT delta-sigma analog-to-digital converters

To date, the development of multifunction multicarrier digital receivers for cellular base station and military communications applications has been limited by the demanding dynamic range requirements for the analog-to-digital converter (ADC). The use of oversampling delta-sigma modulators provides a promising approach to overcoming the dynamic range barriers Nyquist-rate converters face in the same applications. This paper discusses issues involved in the design of high-speed high dynamic range wide-band delta-sigma ADCs for such communications applications. Test results of prototype designs are also presented. The delta-sigma modulators described in this paper operate at sampling frequencies ranging from 1 to 2.5 GHz with center frequencies ranging from dc to 100 MHz, providing between 74 and 84.2 dB signal-to-noise ratio (12 and 13.7 bits) for bandwidths of 25 and 12.5 MHz, respectively. The loop filters are continuous-time low-pass and bandpass implementations of order 6 and 10, and were fabricated in an InP heterojunction bipolar (HBT) technology. A typical tenth-order design consumes 6 W of power and occupies a die area of 23.5 mm/sup 2/.