Orlistat exerts anti-obesity and anti-tumorigenic effects in a transgenic mouse model of endometrial cancer

Introduction: Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models. Methods: In this study, the Lkb1fl/flp53fl/fl mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo. Results: The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer. Discussion: Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity in vivo and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer

Evaluation of different methods of determining the angle of attack on wind turbine blades under yawed inflow conditions

As part of the AVATAR and Mexnext projects, this study compares several methods used to derive lifting line variables from CFD simulations of the MEXICO rotor in yawed inflow. The results from six partners within the AVATAR/Mexnext consortium using five different methods of extraction were compared. Overall comparison of the induced velocities at the mid and tip parts of blade shows fairly good agreement between the tested methods, where the derived angle of attack differs within 1°, within the linear range this accounts to ˂ 10% uncertainty on the aerodynamic forces. The presented comparison shows inadequate agreement between the methods for application towards the root

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Design issues of an IPM motor for EPS

In electric power steering (EPS), permanent magnet (PM) brushless ac (BLAC) motors offer distinct advantages over other electric motor types in terms torque smoothness, reliability and efficiency. The design procedure of an interior permanent magnet (IPM) motor used in EPS is presented in this paper. The requirements of the steering system are first introduced, and the machine's specifications are then derived. Critical issues which have considerable impacts on the machine's performance, such as operation mode, rotor structure and slot/ pole combination, are analyzed. Subsequently, a 12-slot/10-pole sinusoidally excited IPM machine with concentrated windings is proposed and optimized based on finite element analysis (FEA) modelling. The losses and efficiency are then computed. Performance predictions from the FEA results confirm all the requirements are met or exceeded. A prototype motor has been built for validation

Validation of the actuator disc and actuator line techniques for yawed rotor flows using the New MEXICO experimental data

Experimental data acquired in the New MEXICO experiment on a yawed 4.5m diameter rotor model turbine are used here to validate the actuator line (AL) and actuator disc (AD) models implemented in the Large Eddy Simulation code EllipSys3D in terms of loadingand velocity field. Even without modelling the geometry of the hub and nacelle, the AL and AD models produce similar results that are generally in good agreement with the experimental data under the various configurations considered. As expected, the AL model does better at capturing the induction effects from the individual blade tip vortices, while the AD model can reproduce the averaged features of the flow. The importance of using high quality airfoil data (including 3D corrections) as well as a fine grid resolution is highlighted by the results obtained. Overall, it is found that both models can satisfactorily predict the 3D velocity field and blade loading of the New MEXICO rotor under yawed inflow.This work was also supported by the Energy Technology Development and Demonstration Program (EUDP2014, J. nr. 64014-0543) under the Danish Energy Agency.</p