Molecular mechanisms of action and potential biomarkers of growth inhibition of dasatinib (BMS-354825) on hepatocellular carcinoma cells

BACKGROUND: Molecular targeted therapy has emerged as a promising treatment of Hepatocellular carcinoma (HCC). One potential target is the Src family Kinase (SFK). C-Src, a non-receptor tyrosine kinase is a critical link of multiple signal pathways that regulate proliferation, invasion, survival, metastasis, and angiogenesis. In this study, we evaluated the effects of a novel SFK inhibitor, dasatinib (BMS-354825), on SFK/FAK/p130CAS, PI3K/PTEN/Akt/mTOR, Ras/Raf/MAPK and Stats pathways in 9 HCC cell lines. METHODS: Growth inhibition was assessed by MTS assay. EGFR, Src and downstream proteins FAK, Akt, MAPK42/44, Stat3 expressions were measured by western blot. Cell adhesion, migration and invasion were performed with and without dasatinib treatment. RESULTS: The IC(50) of 9 cell lines ranged from 0.7 μM ~ 14.2 μM. In general the growth inhibition by dasatinib was related to total Src (t-Src) and the ratio of activated Src (p-Src) to t-Src. There was good correlation of the sensitivity to dasatinib and the inhibition level of p-Src, p-FAK576/577 and p-Akt. No inhibition was found on Stat3 and MAPK42/44 in all cell lines. The inhibition of cell adhesion, migration and invasion were correlated with p-FAK inhibition. CONCLUSION: Dasatinib inhibits the proliferation, adhesion, migration and invasion of HCC cells in vitro via inhibiting of Src tyrosine kinase and affecting SFK/FAK and PI3K/PTEN/Akt, but not Ras/Raf/MEK/ERK and JAK/Stat pathways. T-Src and p-Src/t-Src may be useful biomarkers to select HCC patients for dasatinib treatment

The free maternal health policy: acceptability and satisfaction with quality of maternal health services during pregnancy in rural Northern Ghana

Introduction: Ghana introduced a maternal health policy in July 2008 to provide free of cost health services to women. However, the utilization of services does not depend on affordability alone but acceptability as well. Acceptability includes attitudes and behaviors of providers and satisfaction with the quality of care. The study explored women’s views and perceptions about attitudes and behaviors of providers and satisfaction with the quality of services under the free maternal health policy in Ghana. In addition, the views and perceptions of providers were examined. Methods: A convergent parallel mixed-methods study was conducted. The study was carried out in the Kassena-Nankana Municipality in Ghana. A structured questionnaire was distributed among women (n=406) who utilized health facilities during pregnancy. Further, focus group discussions (FGDs) with women (n=10) and in-depth interviews with midwives and nurses (n=25) were held. Quantitative data were analyzed using descriptive statistics, while the qualitative data were recorded, transcribed, read, and coded thematically. Results: Women perceived facilities to be clean, especially the smaller ones. Ninety-eight percent of women (n=313/320) perceived providers to be respectful or friendly, and this was mostly confirmed in the FGDs. More than two-thirds of the women (74%, n=300) were also very satisfied or satisfied with the quality of care due to the respect accorded them by providers. Equally, midwives and nurses were satisfied with the quality of care they provided. Nonetheless, providers believed that the unavailability of drugs and supplies, laboratory services, accommodation, and transportation for emergencies reduced women’s satisfaction with services and the quality of care they could provide. Conclusion: The services provided to women during pregnancy were acceptable under the free maternal health policy. There remain challenges in addressing a lack of infrastructure and commodities that affects the quality of care

EFFECTS OF EIGHT-WEEK WHOLE-BODY VIBRATION TRAINING ON POSTURAL STABILITY IN ELDERLY ADULTS

The aim of this study was to examine the effects of an eight-week whole-body vibration training (WBVT) on postural stability (PS) in elderly people. Twenty-two elderly people with normal ability of movement were randomized into the WBVT group (WBVTG, 13 elders), and the control group (CG, 9 elders). The WBVTG underwent WBV training for 8 weeks. The CG did not take any physical training. The PS performance was evaluated by the Biodex Balance System to measure the overall (O), anterior-posterior (AP), and medial-lateral (ML) stability at level 2 (unstable) and level 8 (stable). One-way ANCOVA were used for statistical analysis, with =0.05. Results showed that after training, the WBVG significantly improved the O, AP, and ML stability performance at level 2, and also the O and ML stability performance at level 8

Active Sampling Based on MMD for Model Adaptation

© 2019, ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering. In this paper, we demonstrate a method for transfer learning with minimal supervised information. Recently, researchers have proposed various algorithms to solve transfer learning problems, especially the unsupervised domain adaptation problem. They mainly focus on how to learn a good common representation and use it directly for downstream task. Unfortunately, they ignore the fact that this representation may not capture target-specific feature for target task well. In order to solve this problem, this paper attempts to capture target-specific feature by utilizing labeled data in target domain. Now it’s a challenge that how to seek as little supervised information as possible to achieve good results. To overcome this challenge, we actively select instances for training and model adaptation based on MMD method. In this process, we try to label some valuable target data to capture target-specific feature and fine-tune the classifier networks. We choose a batch of data in target domain far from common representation space and having maximum entropy. The first requirement is helpful to learn a good representation for target domain and the second requirement tries to improve the classifier performance. Finally, we experiment with our method on several datasets which shows significant improvement and competitive advantage against common methods

Quantum state preparation, tomography, and entanglement of mechanical oscillators

Precisely engineered mechanical oscillators keep time, filter signals, and sense motion, making them an indispensable part of today's technological landscape. These unique capabilities motivate bringing mechanical devices into the quantum domain by interfacing them with engineered quantum circuits. Proposals to combine microwave-frequency mechanical resonators with superconducting devices suggest the possibility of powerful quantum acoustic processors. Meanwhile, experiments in several mechanical systems have demonstrated quantum state control and readout, phonon number resolution, and phonon-mediated qubit-qubit interactions. Currently, these acoustic platforms lack processors capable of controlling multiple mechanical oscillators' quantum states with a single qubit, and the rapid quantum non-demolition measurements of mechanical states needed for error correction. Here we use a superconducting qubit to control and read out the quantum state of a pair of nanomechanical resonators. Our device is capable of fast qubit-mechanics swap operations, which we use to deterministically manipulate the mechanical states. By placing the qubit into the strong dispersive regime with both mechanical resonators simultaneously, we determine the resonators' phonon number distributions via Ramsey measurements. Finally, we present quantum tomography of the prepared nonclassical and entangled mechanical states. Our result represents a concrete step toward feedback-based operation of a quantum acoustic processor.Comment: 13 pages, 4+5 figure

Effects of Selfâ Assembled Monolayer Modification of Nickel Oxide Nanoparticles Layer on the Performance and Application of Inverted Perovskite Solar Cells

Entirely lowâ temperature solutionâ processed (â ¤100â °C) planar pâ iâ n perovskite solar cells (PSCs) offer great potential for commercialization of rollâ toâ roll fabricated photovoltaic devices. However, the stable inorganic holeâ transporting layer (HTL) in PSCs is usually processed at high temperature (200â 500â °C), which is far beyond the tolerant temperature (â ¤150â °C) of rollâ toâ roll fabrication. In this context, inorganic NiOx nanoparticles (NPs) are an excellent candidate to serve as the HTL in PSCs, owing to their excellent solution processability at room temperature. However, the lowâ temperature processing condition is usually accompanied with defect formation, which deteriorates the film quality and device efficiency to a large extent. To suppress this setback, we used a series of benzoic acid selfassembled monolayers (SAMs) to passivate the surface defects of the NiOx NPs and found that 4â bromobenzoic acid could effectively play the role of the surface passivation. This SAM layer reduces the trapâ assisted recombination, minimizes the energy offset between the NiOx NPs and perovskite, and changes the HTL surface wettability, thus enhancing the perovskite crystallization, resulting in more stable PSCs with enhanced power conversion efficiency (PCE) of 18.4â %, exceeding the control device PCE (15.5â %). Also, we incorporated the aboveâ mentioned SAMs into flexible PSCs (Fâ PSCs) and achieved one of the highest PCE of 16.2â % on a polyethylene terephthalate (PET) substrate with a remarkable powerâ perâ weight of 26.9â Wâ gâ 1. This facile interfacial engineering method offers great potential for the largeâ scale manufacturing and commercialization of PSCs.Engineered layers: Lowâ temperature solutionâ processed NiOx nanoparticle film is usually accompanied with defect formation. Here, we find that 4â bromobenzoic acid can form a selfâ assembled monolayer (SAM) on the NiOx film and effectively tune the interfacial properties, resulting in high perovskite solar cells (PSCs) efficiency. Also, we incorporate the aboveâ mentioned SAM into flexible PSCsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138886/1/cssc201701262_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138886/2/cssc201701262.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138886/3/cssc201701262-sup-0001-misc_information.pd

Optimum spectral window for imaging of art with optical coherence tomography

Optical Coherence Tomography (OCT) has been shown to have potential for important applications in the field of art conservation and archaeology due to its ability to image subsurface microstructures non-invasively. However, its depth of penetration in painted objects is limited due to the strong scattering properties of artists’ paints. VIS-NIR (400 nm – 2400 nm) reflectance spectra of a wide variety of paints made with historic artists’ pigments have been measured. The best spectral window with which to use optical coherence tomography (OCT) for the imaging of subsurface structure of paintings was found to be around 2.2 μm. The same spectral window would also be most suitable for direct infrared imaging of preparatory sketches under the paint layers. The reflectance spectra from a large sample of chemically verified pigments provide information on the spectral transparency of historic artists’ pigments/paints as well as a reference set of spectra for pigment identification. The results of the paper suggest that broadband sources at ~2 microns are highly desirable for OCT applications in art and potentially material science in general

Satellite-derived Constraints on the Effect of Drought Stress on Biogenic Isoprene Emissions in the Southeast US

While substantial progress has been made to improve our understanding of biogenic isoprene emissions under unstressed conditions, there remain large uncertainties in isoprene emissions under stressed conditions. Here we use the US Drought Monitor (USDM) as a weekly drought severity index and tropospheric columns of formaldehyde (HCHO), the key product of isoprene oxidation, retrieved from the Ozone Monitoring Instrument (OMI) to derive top-down constraints on the response of summertime isoprene emissions to drought stress in the Southeast U.S. (SE US), a region of high isoprene emissions and prone to drought. OMI HCHO column density is found to be 5.3 % (mild drought) &ndash; 19.8 % (severe drought) higher than that in no-drought conditions. A global chemical transport model, GEOS-Chem, with the MEGAN2.1 emission algorithm can simulate this direction of change, but the simulated increases at the corresponding drought levels are 1.4&ndash;2.0 times of OMI HCHO, suggesting the need for a drought-stress algorithm in the model. By minimizing the model-to-OMI differences in HCHO to temperature sensitivity under different drought levels, we derived a top-down drought stress factor (&gamma;d_OMI) in GEOS-Chem that parameterizes using water stress and temperature. The algorithm led to an 8.6 % (mild drought) &ndash; 20.7 % (severe drought) reduction in isoprene emissions in the SE US relative to the simulation without it. With &gamma;d_OMI the model predicts a non-uniform trend of increase in isoprene emissions with drought severity that is consistent with OMI HCHO and a single site&rsquo;s isoprene flux measurements. Compared with a previous drought stress algorithm derived from the latter, the satellite-based drought stress factor performs better in capturing the regional scale drought-isoprene responses as indicated by the close-to-zero mean bias between OMI and simulated HCHO columns under different drought conditions. The drought stress algorithm also reduces the model&rsquo;s high bias in organic aerosols (OA) simulations by 6.60 % (mild drought) to 11.71 % (severe drought) over the SE US compared to the no-stress simulation. The simulated ozone response to the drought stress factor displays a spatial disparity due to the isoprene suppressing effect on oxidants, with an &lt;1 ppb increase in O3 in high-isoprene regions and a 1&ndash;3 ppbv decrease in O3 in low-isoprene regions. This study demonstrates the unique value of exploiting long-term satellite observations to develop empirical stress algorithms on biogenic emissions where in situ flux measurements are limited.</p