DNA-PK-Dependent RPA2 Hyperphosphorylation Facilitates DNA Repair and Suppresses Sister Chromatid Exchange

Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8) has been used as a marker for activation of the DNA damage response. What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s) are responsible for them, and what is the biological outcome of these phosphorylations, however, have not been fully investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks (DSBs) and that the DNA-dependent protein kinase complex (DNA-PK) is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to alanines, which prevent phosphorylations at these sites, caused increased mitotic entry with concomitant increases in RAD51 foci and homologous recombination. Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry. This pathway thus permits cells to repair DNA damage properly and increase cell viability

An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics Approach

BACKGROUND: Simvastatin, which is used to control elevated cholesterol levels, is one of the most widely prescribed drugs. However, a daily excessive dose can induce drug-toxicity, especially in muscle and liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods of toxicity evaluation are desired. METHODOLOGY/PRINCIPAL FINDINGS: As a new way to evaluate toxicity, we performed NMR-based metabonomics analysis of urine samples. Compared to conventional markers, such as AST, ALT, and CK, the urine metabolic profile provided clearer distinction between the pre- and post-treatment groups treated with toxic levels of simvastatin. Through multivariate statistical analysis, we identified marker metabolites associated with the toxicity. Importantly, we observed that the treatment group could be further categorized into two subgroups based on the NMR profiles: weak toxicity (WT) and high toxicity (HT). The distinction between these two groups was confirmed by the enzyme values and histopathological exams. Time-dependent studies showed that the toxicity at 10 days could be reliably predicted from the metabolic profiles at 6 days. CONCLUSIONS/SIGNIFICANCE: This metabonomics approach may provide a non-invasive and effective way to evaluate the simvastatin-induced toxicity in a manner that can complement current measures. The approach is expected to find broader application in other drug-induced toxicity assessments

MEMS Technologies for Energy Harvesting

The objective of this chapter is to introduce the technology of Microelectromechanical Systems, MEMS, and their application to emerging energy harvesting devices. The chapter begins with a general introduction to the most common MEMS fabrication processes. This is followed with a survey of design mechanisms implemented in MEMS energy harvesters to provide nonlinear mechanical actuations. Mechanisms to produce bistable potential will be studied, such as introducing fixed magnets, buckling of beams or using slightly slanted clamped-clamped beams. Other nonlinear mechanisms are studied such as impact energy transfer, or the design of nonlinear springs. Finally, due to their importance in the field of MEMS and their application to energy harvesters, an introduction to actuation using piezoelectric materials is given. Examples of energy harvesters found in the literature using this actuation principle are also presented

Transformative piezoelectric enhancement of P(VDF-TrFE) synergistically driven by nanoscale dimensional reduction and thermal treatment.

Despite the significant potential of organic piezoelectric materials in the electro-mechanical or mechano-electrical applications that require light and flexible material properties, the intrinsically low piezoelectric performance as compared to traditional inorganic materials has limited their full utilization. In this study, we demonstrate that dimensional reduction of poly(vinylidene fluoride trifluoroethylene) (P(VDF-TrFE)) at the nanoscale by electrospinning, combined with an appropriate thermal treatment, induces a transformative enhancement in piezoelectric performance. Specifically, the piezoelectric coefficient (d33) reached up to -108 pm V-1, approaching that of inorganic counterparts. Electrospun mats composed of thermo-treated 30 nm nanofibers with a thickness of 15 μm produced a consistent peak-to-peak voltage of 38.5 V and a power output of 74.1 μW at a strain of 0.26% while sustaining energy production over 10k repeated actuations. The exceptional piezoelectric performance was realized by the enhancement of piezoelectric dipole alignment and the materialization of flexoelectricity, both from the synergistic effects of dimensional reduction and thermal treatment. Our findings suggest that dimensionally controlled and thermally treated electrospun P(VDF-TrFE) nanofibers provide an opportunity to exploit their flexibility and durability for mechanically challenging applications while matching the piezoelectric performance of brittle, inorganic piezoelectric materials

Hybrid tin oxide-SWNT nanostructures based gas sensor

A facile electrochemical functionalization method was utilized to decorate single-walled carbon nanotubes (SWNTs) with tin oxide and their gas sensing performance toward various analytes (NH3, NO2, H-2, H2S, acetone, and water vapor) was evaluated at room temperature. Tin oxy-hydroxide was sitespecifically precipitated on the surface of SWNTs because of an increase in local pH during electrochemical reduction of nitrate to nitrite ions. By adjusting the amount of charge passed during deposition, the amount of tin oxide deposited on SWNTs was controlled, which altered the electronic and gas sensing properties of the nanostructures. The resulting hybrid nanostructures showed excellent sensitivities upon exposure to trace amounts of both oxidizing gases (limit of detection (LOD) of 25 ppbv for NO2) and reducing gases (LOD of 10 ppmv for H-2) at room temperature. The enhanced sensing performance was due to the charge transfer between the surface active tin oxide nanoparticles and SWNTs, with the direction of charge transfer depending on the analyte gas. This approach can be applied to fabricate other hybrid metal oxide-SWNTs nanostructures to create highly sensitive gas sensor arrays. (C) 2013 Elsevier Ltd. All rights reserved