Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells

An improved game-theoretic approach to uncover overlapping communities

How can we uncover overlapping communities from complex networks to understand the inherent structures and functions? Chen et al. firstly proposed a community game (Game) to study this problem, and the overlapping communities have been discovered when the game is convergent. It is based on the assumption that each vertex of the underlying network is a rational game player to maximize its utility. In this paper, we investigate how similar vertices affect the formation of community game. The Adamic–Adar Index (AA Index) has been employed to define the new utility function. This novel method has been evaluated on both synthetic and real-world networks. Experimental study shows that it has significant improvement of accuracy (from 4.8% to 37.6%) compared with the Game on 10 real networks. It is more efficient on Facebook networks (FN) and Amazon co-purchasing networks than on other networks. This result implicates that “friend circles of friends” of Facebook are valuable to understand the overlapping community division

Field trials and test results of portable DVB-T systems with transmit delay diversity

This paper describes work carried out by Brunel University and Broadreach Systems (UK) to quantify the advantages that can be achieved if Transmit Diversity is applied to systems employing the DVB standard. The techniques investigated can be applied to standard receiver equipment without modification. An extensive and carefully planned field trial was performed during the winter of 2007/2008 in Uxbridge (UK) to validate predictions from theoretical modeling and laboratory simulations. The transmissions were performed in the 730 MHz frequency band with a DVB-T transmitter and a mean power of 18.4dBW. Transmit delay diversity has been observed to deliver significant reception improvement in automotive and indoor- non line of sight situations

Fano resonance in a cavity-reflector hybrid system.

© 2017 authors. Published by the American Physical Society.We present the results of transport measurements in a hybrid system consisting of an arch-shaped quantum point contact (QPC) and a reflector; together, they form an electronic cavity in between them. On tuning the arch-QPC and the reflector, an asymmetric resonance peak in resistance is observed at the one-dimension to two-dimension transition. Moreover, a dip in resistance near the pinch-off of the QPC is found to be strongly dependent on the reflector voltage. These two structures fit very well with the Fano line shape. The Fano resonance was found to get weakened on applying a transverse magnetic field, and smeared out at 100 mT. In addition, the Fano-like shape exhibited a strong temperature dependence and gradually smeared out when the temperature was increased from 1.5 to 20 K. The results might be useful in realizing devices for quantum information processing

Associations of physical activity and sedentary behavior during pregnancy with gestational diabetes mellitus among Asian women in Singapore

Background Few studies have investigated physical activity (PA) and sedentary behavior (SB) in relation to fasting (FG) and 2-h postprandial plasma glucose (2hPG) levels and gestational diabetes mellitus (GDM); we investigated these associations among Asian pregnant women. Methods As part of the Growing Up in Singapore Towards healthy Outcomes cohort study, PA and SB (sitting and television times) were assessed by interviewer-administered questionnaire. During 75 g oral glucose tolerance tests at 26–28 weeks’ gestation we measured FG, 2hPG levels and GDM (FG ≥ 7.0 mmol/L and/or 2hPG ≥ 7.8 mmol/L). Associations were analysed by multiple linear and logistic regression. Results Among the 1083 women studied, 18.6% had GDM. SB was not associated with FG, 2hPG and GDM. Higher categories of PA were associated with lower 2hPG and a lower likelihood of GDM (p-trend < 0.05), but not with FG levels. Compared to insufficiently active women, highly active women had lower 2hPG levels [β (95% CI): -0.32 (−0.59, −0.05), p = 0.020) and were less likely to have GDM [OR: 0.56 (0.32–0.98), p = 0.040]. Stratified analysis revealed no associations among under/normal-weight women, but significant associations among overweight/obese women; in those with BMI ≥23 kg/m2, sufficiently active and highly active women were less likely to have GDM [OR: 0.52, (0.29–0.93), p = 0.028, and OR: 0.34, (0.15–0.77), p = 0.010, respectively]. Conclusion Higher PA was associated with lower 2hPG levels and a lower prevalence of GDM, particularly in overweight/obese women. Further studies are warranted to confirm these findings, and to examine the effectiveness of PA promotion strategies for the prevention of gestational hyperglycemia

Method for Generating Additive Shape Invariant Potentials from an Euler Equation

In the supersymmetric quantum mechanics formalism, the shape invariance condition provides a sufficient constraint to make a quantum mechanical problem solvable; i.e., we can determine its eigenvalues and eigenfunctions algebraically. Since shape invariance relates superpotentials and their derivatives at two different values of the parameter $a$, it is a non-local condition in the coordinate-parameter $(x, a)$ space. We transform the shape invariance condition for additive shape invariant superpotentials into two local partial differential equations. One of these equations is equivalent to the one-dimensional Euler equation expressing momentum conservation for inviscid fluid flow. The second equation provides the constraint that helps us determine unique solutions. We solve these equations to generate the set of all known $\hbar$-independent shape invariant superpotentials and show that there are no others. We then develop an algorithm for generating additive shape invariant superpotentials including those that depend on $\hbar$ explicitly, and derive a new $\hbar$-dependent superpotential by expanding a Scarf superpotential.Comment: 1 figure, 4 tables, 18 page

Bayesian model averaging: improved variable selection for matched case-control studies

Background: The problem of variable selection for risk factor modeling is an ongoing challenge in statistical practice. Classical methods that select one subset of exploratory risk factors dominate the medical research field. However, this approach has been criticized for not taking into account the uncertainty of the model selection process itself. This limitation can be addressed by a Bayesian model averaging approach: instead of focusing on a single model and a few factors, Bayesian model averaging considers all the models with non-negligible probabilities to make inference. Methods: This paper reports on a simulation study designed to emulate a matched case-control study and compares classical versus Bayesian model averaging selection methods. We used Matthews’s correlation coefficient to measure the quality of binary classifications. Both classical and Bayesian model averaging were also applied and compared for the analysis of a matched case-control study of patients with methicillin-resistant Staphylococcus aureus infections after hospital discharge 2011-2013. Results: Bayesian model averaging outperformed the classical approach with much lower false positive rates and higher Matthew’s correlation scores. Bayesian model averaging also produced more reliable and robust effect estimates. Conclusion: Bayesian model averaging is a conceptually simple, unified approach that produces robust results. It can be used to replace controversial P-values for case-control study in medical research