The BRG-1 Subunit of the SWI/SNF Complex Regulates CD44 Expression

Aberrant regulation of CD44, a transmembrane glycoprotein, has been implicated in the growth and metastasis of numerous tumors. Although both CD44 overexpression and loss have been implicated in tumor progression, the mechanism of CD44 down-regulation in these tumor types is not known. By immunoblot and reverse transcription-polymerase chain reaction analysis we determined that a cervical carcinoma cell line, C33A, lacks CD44 expression. To determine how CD44 is down-regulated in C33A cells, we utilized cell fusions of C33A cells with a CD44-expressing cell line (SAOS-2). We found that SAOS-2 fusion restored CD44 expression in C33A cells, suggesting that a trans-acting factor present in SAOS-2 cells promotes CD44 production. C33A cells are BRG-1-deficient, and we found that CD44 was absent in another BRG-1-deficient tumor cell line, indicating that loss of BRG-1 may be a general mechanism by which cells lose CD44. Reintroduction of BRG-1 into these cells restored CD44 expression. Furthermore, disruption of BRG-1 function through the use of dominant-negative BRG-1 demonstrated the requirement of BRG-1 in CD44 regulation. Finally, we show that Cyclin E overexpression resulted in the attenuation of CD44 stimulation, which is consistent with previous observations that Cyclin E can abrogate BRG-1 action. Taken together, these results suggest that BRG-1 is a critical regulator of CD44 expression, thus implicating SWI/SNF components in the regulation of cellular adhesion and metastasis

Prominent radiative contributions from multiply-excited states in laser-produced tin plasma for nanolithography

Extreme ultraviolet (EUV) lithography is currently entering high-volume manufacturing to enable the continued miniaturization of semiconductor devices. The required EUV light, at 13.5 nm wavelength, is produced in a hot and dense laser-driven tin plasma. The atomic origins of this light are demonstrably poorly understood. Here we calculate detailed tin opacity spectra using the Los Alamos atomic physics suite ATOMIC and validate these calculations with experimental comparisons. Our key finding is that EUV light largely originates from transitions between multiply-excited states, and not from the singly-excited states decaying to the ground state as is the current paradigm. Moreover, we find that transitions between these multiply-excited states also contribute in the same narrow window around 13.5 nm as those originating from singly-excited states, and this striking property holds over a wide range of charge states. We thus reveal the doubly magic behavior of tin and the origins of the EUV light

Imprinted CDKN1C Is a Tumor Suppressor in Rhabdoid Tumor and Activated by Restoration of SMARCB1 and Histone Deacetylase Inhibitors

SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor

Photoluminescence-based detection of particle contamination on extreme ultraviolet reticles

Here, we propose a comparison-free inspection technique to detect particle contamination on the reticle of extreme ultraviolet (EUV) lithography systems, based on the photoluminescence spectral characteristics of the contaminant particles and their elemental composition. We have analyzed the spectra from different particles found on reticles in EUV lithographic systems and have determined the minimum detectable particle size: 25 nm for organic particles and 100 nm for Al particles. Stainless steel coatings (50 nm thick and 50 × 50 μm2 in area) exhibit detectable photoluminescence, and the estimated minimum detectable particle is 2 μm

Extreme ultraviolet induced defects on few-layer graphene

We use Raman spectroscopy to show that exposing few-layer graphene to extreme ultraviolet (EUV, 13.5 nm) radiation, i.e., relatively low photon energy, results in an increasing density of defects. Furthermore, exposure to EUV radiation in a H2 background increases the graphene dosage sensitivity, due to reactions caused by the EUV induced hydrogen plasma. X-ray photoelectron spectroscopy results show that the sp2 bonded carbon fraction decreases while the sp3 bonded carbon and oxide fraction increases with exposure dose. Our experimental results confirm that even in reducing environment oxidation is still one of the main source of inducing defects. © 2013 AIP Publishing LLC

Extreme Ultraviolet (EUV) induced defects on few-layer graphene

We use Raman spectroscopy to show that exposing few-layer graphene to extreme ultraviolet (EUV, 13.5 nm) radiation, i.e., relatively low photon energy, results in an increasing density of defects. Furthermore, exposure to EUV radiation in a H2 background increases the graphene dosage sensitivity, due to reactions caused by the EUV induced hydrogen plasma. X-ray photoelectron spectroscopy results show that the sp2 bonded carbon fraction decreases while the sp3 bonded carbon and oxide fraction increases with exposure dose. Our experimental results confirm that even in reducing environment oxidation is still one of the main source of inducing defects

Extreme ultraviolet induced defects on few-layer graphene

We use Raman spectroscopy to show that exposing few-layer graphene to extreme ultraviolet (EUV, 13.5 nm) radiation, i.e., relatively low photon energy, results in an increasing density of defects. Furthermore, exposure to EUV radiation in a H2 background increases the graphene dosage sensitivity, due to reactions caused by the EUV induced hydrogen plasma. X-ray photoelectron spectroscopy results show that the sp2 bonded carbon fraction decreases while the sp3 bonded carbon and oxide fraction increases with exposure dose. Our experimental results confirm that even in reducing environment oxidation is still one of the main source of inducing defects. © 2013 AIP Publishing LLC