105 research outputs found
NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines
<p>Abstract</p> <p>Background</p> <p>YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas.</p> <p>Results</p> <p>We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines). Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells.</p> <p>Conclusion</p> <p>These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.</p
Reconstructing the properties of dark energy from recent observations
We explore the properties of dark energy from recent observational data,
including the Gold Sne Ia, the baryonic acoustic oscillation peak from SDSS,
the CMB shift parameter from WMAP3, the X-ray gas mass fraction in cluster and
the Hubble parameter versus redshift. The model with curvature
and two parameterized dark energy models are studied. For the
model, we find that the flat universe is consistent with observations at the
confidence level and a closed universe is slightly favored by these
data. For two parameterized dark energy models, with the prior given on the
present matter density, , with ,
and , our result seems to suggest that the
trend of dependence for an evolving dark energy from a
combination of the observational data sets is model-dependent.Comment: 16 pages, 15 figures, To appear in JCA
Anomalous stopping of laser-accelerated intense proton beam in dense ionized matter
Ultrahigh-intensity lasers (10-10W/cm) have opened up new
perspectives in many fields of research and application [1-5]. By irradiating a
thin foil, an ultrahigh accelerating field (10 V/m) can be formed and
multi-MeV ions with unprecedentedly high intensity (10A/cm) in short
time scale (ps) are produced [6-14]. Such beams provide new options in
radiography [15], high-yield neutron sources [16], high-energy-density-matter
generation [17], and ion fast ignition [18,19]. An accurate understanding of
the nonlinear behavior of beam transport in matter is crucial for all these
applications. We report here the first experimental evidence of anomalous
stopping of a laser-generated high-current proton beam in well-characterized
dense ionized matter. The observed stopping power is one order of magnitude
higher than single-particle slowing-down theory predictions. We attribute this
phenomenon to collective effects where the intense beam drives an decelerating
electric field approaching 1GV/m in the dense ionized matter. This finding will
have considerable impact on the future path to inertial fusion energy.Comment: 8 pages, 4 figure
Energy loss enhancement of very intense proton beams in dense matter due to the beam-density effect
Thoroughly understanding the transport and energy loss of intense ion beams
in dense matter is essential for high-energy-density physics and inertial
confinement fusion. Here, we report a stopping power experiment with a
high-intensity laser-driven proton beam in cold, dense matter. The measured
energy loss is one order of magnitude higher than the expectation of individual
particle stopping models. We attribute this finding to the proximity of beam
ions to each other, which is usually insignificant for relatively-low-current
beams from classical accelerators. The ionization of the cold target by the
intense ion beam is important for the stopping power calculation and has been
considered using proper ionization cross section data. Final theoretical values
agree well with the experimental results. Additionally, we extend the stopping
power calculation for intense ion beams to plasma scenario based on Ohm's law.
Both the proximity- and the Ohmic effect can enhance the energy loss of intense
beams in dense matter, which are also summarized as the beam-density effect.
This finding is useful for the stopping power estimation of intense beams and
significant to fast ignition fusion driven by intense ion beams
Long-Term ERK Inhibition in
Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in -mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of -mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified. Unexpectedly, long-term treatment of sensitive cell lines caused senescence, mediated in part by MYC degradation and p16 reactivation. Enhanced basal PI3K-AKT-mTOR signaling was associated with de novo resistance to ERK inhibitor, as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-function screen. Our findings reveal distinct consequences of inhibiting this kinase cascade at the level of ERK
Facile Synthesis of Monodisperse CdS Nanocrystals via Microreaction
CdS-based nanocrystals (NCs) have attracted extensive interest due to their potential application as key luminescent materials for blue and white LEDs. In this research, the continuous synthesis of monodisperse CdS NCs was demonstrated utilizing a capillary microreactor. The enhanced heat and mass transfer in the microreactor was useful to reduce the reaction temperature and residence time to synthesize monodisperse CdS NCs. The superior stability of the microreactor and its continuous operation allowed the investigation of synthesis parameters with high efficiency. Reaction temperature was found to be a key parameter for balancing the reactivity of CdS precursors, while residence time was shown to be an important factor that governs the size and size distribution of the CdS NCs. Furthermore, variation of OA concentration was demonstrated to be a facile tuning mechanism for controlling the size of the CdS NCs. The variation of the volume percentage of OA from 10.5 to 51.2% and the variation of the residence time from 17 to 136 s facilitated the synthesis of monodisperse CdS NCs in the size range of 3.0–5.4 nm, and the NCs produced photoluminescent emissions in the range of 391–463 nm
Target density effects on charge tansfer of laser-accelerated carbon ions in dense plasma
We report on charge state measurements of laser-accelerated carbon ions in
the energy range of several MeV penetrating a dense partially ionized plasma.
The plasma was generated by irradiation of a foam target with laser-induced
hohlraum radiation in the soft X-ray regime. We used the tri-cellulose acetate
(CHO) foam of 2 mg/cm density, and -mm interaction
length as target material. This kind of plasma is advantageous for
high-precision measurements, due to good uniformity and long lifetime compared
to the ion pulse length and the interaction duration. The plasma parameters
were diagnosed to be T=17 eV and n=4 10 cm.
The average charge states passing through the plasma were observed to be higher
than those predicted by the commonly-used semiempirical formula. Through
solving the rate equations, we attribute the enhancement to the target density
effects which will increase the ionization rates on one hand and reduce the
electron capture rates on the other hand. In previsous measurement with
partially ionized plasma from gas discharge and z-pinch to laser direct
irradiation, no target density effects were ever demonstrated. For the first
time, we were able to experimentally prove that target density effects start to
play a significant role in plasma near the critical density of Nd-Glass laser
radiation. The finding is important for heavy ion beam driven high energy
density physics and fast ignitions.Comment: 7 pages, 4 figures, 35 conference
Synthesis of Monodisperse Nanocrystals via Microreaction: Open-to-Air Synthesis with Oleylamine as a Coligand
Microreaction provides a controllable tool to synthesize CdSe nanocrystals (NCs) in an accelerated fashion. However, the surface traps created during the fast growth usually result in low photoluminescence (PL) efficiency for the formed products. Herein, the reproducible synthesis of highly luminescent CdSe NCs directly in open air was reported, with a microreactor as the controllable reaction tool. Spectra investigation elucidated that applying OLA both in Se and Cd stock solutions could advantageously promote the diffusion between the two precursors, resulting in narrow full-width-at-half maximum (FWHM) of PL (26 nm). Meanwhile, the addition of OLA in the source solution was demonstrated helpful to improve the reactivity of Cd monomer. In this case, the focus of size distribution was accomplished during the early reaction stage. Furthermore, if the volume percentage (vol.%) of OLA in the precursors exceeded a threshold of 37.5%, the resulted CdSe NCs demonstrated long-term fixing of size distribution up to 300 s. The observed phenomena facilitated the preparation of a size series of monodisperse CdSe NCs merely by the variation of residence time. With the volume percentage of OLA as 37.5% in the source solution, a 78 nm tuning of PL spectra (from 507 to 585) was obtained through the variation of residence time from 2 s to 160 s, while maintaining narrow FMWH of PL (26–31 nm) and high QY of PL (35–55%)
A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice
Many genetic liver diseases present in newborns with repeated, often lethal, metabolic crises. Gene therapy using non-integrating viruses such as AAV is not optimal in this setting because the non-integrating genome is lost as developing hepatocytes proliferate1,2. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR/Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7% – 20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet
- …