Cancer cells undergoing epigenetic transition show short-term resistance and are transformed into cells with medium-term resistance by drug treatment

To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2–3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.Subject terms: Tumour heterogeneity, Epigenetics     

Runaway Electron Measurements in the EAST Tokamak

An experimental study of runaway electrons in the EAST tokamak has been performed by a recently developed multi‐channel hard x‐ray diagnostics based on NaI(TL) scintillator detectors. It is found that in the current quench phase, the inductive loop voltage plays an important role in the generation of runaway electrons. And the avalanche mechanism was the main mechanism for runaway electrons after the disruptions. The distribution and transportation of runaway electrons were also investigated by multi‐channel hard x‐ray diagnostics. It is also found that the intensity of runaway electrons emission in the core plasma was much higher than those in the downside of the cross‐section, while the emission intensity of runaway electrons in the core plasma was almost the same. Calculated shrinking coefficient of runaway electrons emission after the plasma disruption was about 26 m/s according to the experimental data (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Fabrication of monodisperse silica-polymer core-shell nanoparticles with excellent antimicrobial efficacy

Monodisperse nanoparticles with antimicrobial polymer shells were fabricated using a seeded copolymerization; they exhibited excellent antibacterial activities against gram-positive bacteria as well as gram-negative bacteria.     

Observation of Runaway Electron Behaviour During Disruptions in LHCD Discharges in the HT‐7 Tokamak

Production of runaway electrons during disruptions has been observed in the HT‐7 Tokamak. The runaway current plateaus, which can carry part of the pre‐disruptive current, are observed in lower‐hybrid current drive (LHCD) limiter discharges. It is found that the runaway current can mitigate the disruptions effectively. We can use gas puffing to increase the line‐averaged density to restrain the runaway electrons and rebuild the plasmas after the disruptions. Detailed observations are presented on the runaway electrons generated following disruptions in the HT‐7 tokamak discharges. The results indicate that the magnetic oscillations play a significant role in the loss of runaway electrons in disruptions. There are two important preconditions to rebuild plasmas by runaway electrons after the disruptions. One of them are weak magnetic oscillations; another one are LHWs (lower‐hybrid waves) (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Forward-reflected-backward method with variance reduction

Computational Optimization and Applications - We propose a variance reduced algorithm for solving monotone variational inequalities. Without assuming strong monotonicity, cocoercivity, or...     

Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis

Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp(2)-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- and β-Gal associated with Fabry disease and GM(1) gangliosidosis.     

Low Earth orbit satellite-to-ground optical scintillation: comparison of experimental observations and theoretical predictions

Scintillation measurements of a 1064 nm laser at a 5 kHz sampling rate were made by an optical ground station at the European Space Agency observatory in Tenerife, Spain while tracking a low Earth orbit satellite during the spring and summer of 2010. The scintillation index (SI), the variance of irradiance normalized to the square of the mean, and power spectra measurements were compared to theoretical predictions based on the Kolmogorov spectrum, the Maui3 nighttime turbulence profile, weak scintillation finite-beam wave theory, included receiver, and source aperture averaging with no free-fitting parameters. Good agreement was obtained, not only for the magnitude of the observed fluctuations, but also for the corresponding elevation angle dependence and shape of the power spectra. Little variation was seen for the SI between daytime and nighttime links. For all elevation angles, ascending and descending, the observed scintillation over extensive regions of the atmosphere is consistent with log-normal statistics. Additionally, it appears from the results presented here that the nighttime turbulence profile for the atmosphere above the observatory in Tenerife is similar to that above Haleakala in Maui, Hawaii.     

Engineered Functional Recovery of Microbial Rhodopsin Without Retinal‐Binding Lysine

Definition of rhodopsin is the retinal‐binding membrane protein with the Schiff base linkage at a lysine on the 7^th transmembrane helix. However, ~ 600 microbial rhodopsins lack retinal‐binding lysine at the corresponding position (Rh‐noK) among ~ 5500 known microbial rhodopsins, suggesting that Rh‐noK has each functional role without chromophore. Here, we report successful functional recovery of Rh‐noK. Two Rh‐noKs from bacteria were heterologously expressed in Escherichia coli, which exhibited no color. When retinal‐binding lysine was introduced, one of them gained visible color. Additional mutation of the Schiff base counterion further gained proton‐pumping activity. Successful engineered functional recovery such as visible color and proton‐pump activity suggests that the Rh‐noK protein forms a characteristic structure of microbial rhodopsins.