The glass transition temperatures (Tg's) of ultrathin films (thickness 80-18 nm) of polystyrene (PS) and poly(methyl methacrylate) (PMMA) were measured on surfaces with interfacial energies (γSL) ranging from 0.50 to 6.48 mJ/m 2 . The surfaces consisted of self-assembled films of octadecyltrichlorosilane (OTS) that were exposed to X-rays in the presence of air. Exposure to X-ray radiation systematically modified the OTS by incorporating oxygen-containing groups on the surface. The interfacial energy for PS and PMMA on the OTS surface was quantified as a function of X-ray dose using the Fowkes-van Oss-Chaudhury-Good model of surface tension. The T g values of the films were characterized by three complementary techniques: local thermal analysis, ellipsometry, and X-ray reflectivity. Within the resolution of the techniques, the results were in agreement. At low values of γSL, the Tg values of PS and PMMA films were below the respective bulk values of the polymers. At high values of γSL, the Tg values of PS and PMMA films were higher than the bulk values and increased monotonically with increasing γSL. The deviation of the Tg values of the films compared to the bulk values increased with decreasing film thickness. For a specific film thickness of PS and PMMA, the difference between the Tg of the film and Tg of the bulk polymer (∆Tg ) Tg film -Tg bulk ) scaled linearly with γSL irrespective of the chemistry of the polymer.

The nitrogen solubilities in liquid manganese, manganese-iron, manganese-carbon, and manganeseiron-carbon alloys have been measured by the gas-liquid metal equilibration technique in the temperature range of 1623 to 1823 K. The equilibrium nitrogen content in pure liquid manganese at an atmospheric nitrogen pressure is high, and it does not follow Sievert's law, i.e., f N is not unity. The reduced nitrogen partial pressures by dilution with argon enabled us to obtain more reliable information on the thermodynamics of nitrogen in liquid manganese. The nitrogen dissolution follows Sievert's law at nitrogen contents below 1 wt pct. The standard free-energy change for the dissolution of nitrogen in pure liquid manganese has been determined as Ϫ67,222 ϩ 30.32T J/g atom, with the standard state of nitrogen taken as a 1 wt pct solution. Carbon and iron in manganese-rich melts decrease the nitrogen solubility significantly. The first-and second-order interaction parameters between nitrogen and other elements in manganese alloy melts have been determined. The activity coefficient of nitrogen in a ferromanganese alloy melt can be expressed as log f N ϭ 0.005 (pct N) ϩ 0.029 (pct N) 2 ϩ 0.015 (pct Fe) ϩ 0.09 (pct C) ϩ 0.013 (pct C) 2 where the interaction parameters are independent of temperature in the temperature range of 1623 to 1823 K.

BackgroundThe ataxia–telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells.MethodsLung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue.ResultsTransient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis.ConclusionscAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.

Background: cAMP signaling augments radiation-induced apoptosis of lung cancer cells. Results: cAMP signaling reduces the expression of sirtuin 6 deacetylase in non-small cell lung cancer cells by promoting ubiquitin-proteasomal degradation via inhibition of the Raf-MEK-ERK pathway. Conclusion: cAMP signaling reduces sirtuin 6, which augments radiation-induced apoptosis in lung cancer cells. Significance: cAMP signaling augments radiation-induced apoptosis by modulating epigenetic control.

CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.