608 research outputs found
Nanoscale damage during fracture in silica glass
We report here atomic force microscopy experiments designed to uncover the
nature of failure mechanisms occuring within the process zone at the tip of a
crack propagating into a silica glass specimen under stress corrosion. The
crack propagates through the growth and coalescence of nanoscale damage spots.
This cavitation process is shown to be the key mechanism responsible for damage
spreading within the process zone. The possible origin of the nucleation of
cavities, as well as the implications on the selection of both the cavity size
at coalescence and the process zone extension are finally discussed.Comment: 12 page
Inelastic interaction mean free path of negative pions in tungsten
The inelastic interaction mean free paths lambda of 5, 10, and 15 GeV/c pions were measured by determining the distribution of first interaction locations in a modular tungsten-scintillator ionization spectrometer. In addition to commonly used interaction signatures of a few (2-5) particles in two or three consecutive modules, a chi2 distribution is used to calculate the probability that the first interaction occurred at a specific depth in the spectrometer. This latter technique seems to be more reliable than use of the simpler criteria. No significant dependence of lambda on energy was observed. In tungsten, lambda for pions is 206 plus or minus 6 g/sq cm
Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations
The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors
Results from the first use of low radioactivity argon in a dark matter search
Liquid argon is a bright scintillator with potent particle identification
properties, making it an attractive target for direct-detection dark matter
searches. The DarkSide-50 dark matter search here reports the first WIMP search
results obtained using a target of low-radioactivity argon. DarkSide-50 is a
dark matter detector, using two-phase liquid argon time projection chamber,
located at the Laboratori Nazionali del Gran Sasso. The underground argon is
shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3
relative to atmospheric argon. We report a background-free null result from
(2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with
our previous search using an atmospheric argon, the 90 % C.L. upper limit on
the WIMP-nucleon spin-independent cross section based on zero events found in
the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43
cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.
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Measurement of geo-neutrinos from 1353 days of Borexino
We present a measurement of the geo--neutrino signal obtained from 1353 days
of data with the Borexino detector at Laboratori Nazionali del Gran Sasso in
Italy. With a fiducial exposure of (3.69 0.16) proton
year after all selection cuts and background subtraction, we detected
(14.3 4.4) geo-neutrino events assuming a fixed chondritic mass Th/U
ratio of 3.9. This corresponds to a geo-neutrino signal = (38.8
12.0) TNU with just a 6 probability for a null geo-neutrino
measurement. With U and Th left as free parameters in the fit, the relative
signals are = (10.6 12.7) TNU and =
(26.5 19.5) TNU. Borexino data alone are compatible with a mantle
geo--neutrino signal of (15.4 12.3) TNU, while a combined analysis with
the KamLAND data allows to extract a mantle signal of (14.1 8.1) TNU. Our
measurement of a reactor anti--neutrino signal =
84.5 TNU is in agreement with expectations in the presence of
neutrino oscillations.Comment: 9 pages, 6 figure
Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear receptor SHP
Dnmt1 is frequently overexpressed in cancers, which contributes significantly to cancer-associated epigenetic silencing of tumor suppressor genes. However, the mechanism of Dnmt1 overexpression remains elusive. Herein, we elucidate a pathway through which nuclear receptor SHP inhibits zinc-dependent induction of Dnmt1 by antagonizing metal-responsive transcription factor-1 (MTF-1). Zinc treatment induces Dnmt1 transcription by increasing the occupancy of MTF-1 on the Dnmt1 promoter while decreasing SHP expression. SHP in turn represses MTF-1 expression and abolishes zinc-mediated changes in the chromatin configuration of the Dnmt1 promoter. Dnmt1 expression is increased in SHP-knockout (sko) mice but decreased in SHP-transgenic (stg) mice. In human hepatocellular carcinoma (HCC), increased DNMT1 expression is negatively correlated with SHP levels. Our study provides a molecular explanation for increased Dnmt1 expression in HCC and highlights SHP as a potential therapeutic target
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