The molecular mechanisms controlling post-translational modifications of p21 have been pursued assiduously in recent years. Here, utilizing mass-spectrometry analysis and site-specific acetyl-p21 antibody, two lysine residues of p21, located at aminoacid sites 161 and 163, were identified as Tip60-mediated acetylation targets for the first time. Detection of adriamycin-induced p21 acetylation, which disappeared after Tip60 depletion with concomitant destabilization of p21 and disruption of G1 arrest, suggested that Tip60-mediated p21 acetylation is necessary for DNA damage-induced cell-cycle regulation. The ability of 2KQ, a mimetic of acetylated p21, to induce cell-cycle arrest and senescence was significantly enhanced in p21 null MEFs compared with those of cells expressing wild-type p21. Together, these observations demonstrate that Tip60-mediated p21 acetylation is a novel and essential regulatory process required for p21-dependent DNA damage-induced cell-cycle arrest. A plethora of cellular perturbations stimulate cells to halt their growth progression by activating numerous cell-cycle inhibitors and apoptotic factors. Among these, p21 is a key member whose major function is to suppress the activities of cyclindependent kinases (CDKs).1,2 This, in turn, leads to cellular growth arrest at a certain stage of the cell cycle mainly as a result of the inhibition of RB or cyclin B phosphorylation. 2-4The induction of p21 requires the presence of p53, a potent tumor suppressor, as its major transcriptional regulator. 5,6 In addition to transcriptional regulation, a variety of regulatory proteins that modulate the activity of p21 in its posttranslational stage have been characterized. 7-13 For example, several E3 ligases, including CUL1, CUL4, and APC2 complexes, function to constitutively induce destabilization of p21 and facilitate cell-cycle progress.9 In addition to these ligases, p21 levels are closely monitored under normal cellular conditions by other E3 ligases, such as MKRN1, p53RFP, and RNF126, in order to facilitate senescent-free progression. 11,13,14 The interaction of histone deacetylases (HDACs) with p21 was also identified in a recent study, suggesting a possible acetylation process for p21. 15Tip60, originally identified as HIV-1 interacting acetyltransferase, is a member of the MYST family, which contains MOZ, Ybf2/Sas2, and Sas2 motifs. 16,17 Tip60-mediated acetylation of H2AX, a member of the histone family of proteins that plays a major role in DNA repair, helps to enhance DNA dynamics upon DNA-damaging stresses. 18,19 On the other hand, nonhistone proteins targeted by Tip60 include ATM, p53, and Myc, among others. 20,21 Tip60 can mediate the acetylation of p53 at the lysine residue 120, resulting in increased p53 transcriptional activity with the induction of PUMA and BAX. 22,23 Several studies have reported that the acetylase activity of Tip60 is enhanced by various stresses such as ER stress, serum deprivation, and DNA damage, including damage due to ionizing radiation and UV irradiation. 24...

Active modulation of ions and molecules via field-effect gating in nanofluidic channels is a crucial technology for various promising applications such as DNA sequencing, drug delivery, desalination, and energy conversion. Developing a rapid and facile fabrication method for ionic field-effect transistors (FET) over a large area may offer exciting opportunities for both fundamental research and innovative applications. Here, we report a rapid, cost-effective route for the fabrication of large-scale nanofluidic field-effect transistors using a simple, lithography-free two-step fabrication process that consists of sputtering and barrier-type anodization. A robust alumina gate dielectric layer, which is formed by anodizing sputtered aluminium, can be rapidly fabricated in the order of minutes. When anodizing aluminium, we employ a hemispherical counter electrode in order to give a uniform electric field that encompasses the whole sputtered aluminium layer which has high surface roughness. In consequence, a well-defined thin layer of alumina with perfect step coverage is formed on a highly rough aluminium surface. A gate-all-around nanofluidic FET with a leak-free gate dielectric exhibits outstanding gating performance despite a large channel size. The thin and robust anodized alumina gate dielectric plays a crucial role in achieving such excellent capacitive coupling. The combination of a gate-all-around structure with a leak-free gate dielectric over a large area could yield breakthroughs in areas ranging from biotechnology to energy and environmental applications.

We report the thermal conductivities of Ge1Sb4Te7 and nitrogen-doped Ge1Sb4Te7 thin films at temperatures ranging from 300 to 520 K using the 3ω method. Thermal conductivity of Ge1Sb4Te7 increases abruptly during the transition from the amorphous to crystalline phase. Nitrogen doping effectively suppresses the crystallization process, resulting reduction of lattice as well as electronic thermal conductivity. These behaviors are confirmed by x-ray diffraction, sheet conductance, and thermal conductivity measurements. Numerical modeling of phase change memory device shows that with nitrogen doping, performance increase in terms of lower reset current and faster reset time can be achieved.

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