Overexpression of β1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma

© Liu et al. Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed that overexpression of β1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of β1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that β1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comparing automated vehicles with human drivers: Improving motion comfort with motion planning and suspension control

This dissertation is dedicated to understanding the potential of improving the motion comfort of automated vehicles and explores multiple options that serve this purpose. Comfort is usually prioritized behind factors such as safety and efficiency but is nevertheless influential to the acceptance of automated vehicles. The goal of enhancing motion comfort overlaps with the need to overcome challenges brought by the motion sickness phenomenon. Motion sickness is found to impact a significant portion of travelers in all types of transport. It tends to develop faster among occupants who are not engaged in the driving task. Its symptoms can cause difficulties for non-driving-related tasks (NDRTs) to be performed effectively by the passengers. Therefore, a part of the research in this dissertation is directed specifically toward mitigating motion sickness in automated vehicles...Intelligent Vehicle

Virtual Inertia Emulation in islanded microgrids with energy storage system

The inertial response plays a vital role in electrical networks to reduce the rate of change of frequency (RoCoF) following a contingency event. If the inertia has a low or zero value due to a lack of synchronous generators, then the electrical network might experience large undesirable frequency deviations. To overcome this problem, in previous research, mathematical methods have been emerged to enhance the system stability in current source based microgrids. The battery energy storage system embodies the isolated microgrid operates as voltage source and the implementation of the demand side management in which frequency is used as a communication signal. The requirement for inertia frequency response is indicated. In this work, the power electronics methods to emulate virtual inertia have been found, developed and compared. An overview of existing methods has been presented, which includes the introduction of the principles and comparison between their advantages and disadvantages. Based on those techniques, an additional PID controller has been recommended for the isolated microgrids working as current source. Furthermore, three control schemes to incite inertial responses have been developed for the microgrids in voltage source type as follows: 1) swing equation method, 2) low pass filter, and 3) an adjustable rate limiter. introducing swing equation, adding low-pass filter and setting rate limiter.Electrical Engineering, Mathematics and Computer ScienceElectrical Sustainable Energ

A real-time nonlinear MPC for extreme lateral stabilization of passenger vehicles

Loss of lateral stability remains a major cause of road accidents in recent years. Further improvement of passenger vehicle's active safety requires a more efficient utilization of the tire-road friction. Nonlinear model predictive control (NMPC) is expected to fulfill such a role, as the nonlinear characteristics of the vehicle are included and the control input is optimized. However, the computational load can be excessive for onboard hardware, which hinders the NMPC from practical implementation. To tackle the problem, this study proposes a method to improve the computational efficiency in NMPC. The proposed solution consists of an explicitly stored look-up table for generating initial guesses and an online optimization component. The look-up table is based on the offline solution of a hybrid MPC controller. Through the simulation with multibody vehicle model, impressive control performance has been observed, as the vehicle can be stabilized from a side-slip angle of up to 0.5 rad.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Intelligent Vehicle

Minimizing readout-induced noise for early fault-tolerant quantum computers

Quantum error correcting code can diagnose potential errors and correct them based on measured outcomes by leveraging syndrome measurement. However, mid-circuit measurement has been technically challenging for early fault-tolerant quantum computers and the readout-induced noise acts as a main contributor to the logical infidelity. We present a different method for syndrome extraction, namely generalized syndrome measurement, that requires only a single-shot measurement on a single ancilla, while the canonical syndrome measurement requires multiple measurements to extract the eigenvalue for each stabilizer generator. As such, we can detect the error in the logical state with minimized readout-induced noise. By adopting our method as a precheck routine for quantum error correcting cycles, we can significantly reduce the readout overhead, the idling time, and the logical error rate during syndrome measurement. We numerically analyze the performance of our protocol using Iceberg code and Steane code under realistic noise parameters based on superconducting hardware and demonstrate the advantage of our protocol in the near-term scenario. As mid-circuit measurements are still error-prone for near-term quantum hardware, our method could boost the applications of early fault-tolerant quantum computing.QID/Borregaard Grou

Historical Canals as Urban Landscape Infrastructure in Guangzhou: Reactivating Public Life Through Water

In the heart of the Pearl River Delta, the city of Guangzhou is fast-growing and prone to flooding. In history, people constructed canals based on natural waterways to deal with water problems. The canal system not only served as an important infrastructure but was also as the backbone of urban life. But with the development of the road network in recent decades, the urban canals in the historical inner city have been neglected and are disappearing, losing their identity, and becoming the forgotten side of the city. What can be learned from the historical situation to reactivate the urban canals as carriers of socially and ecologically inclusive urban space? This chapter aims to identify design principles for (historical) urban canal design and examine their potential through design exploration, with Donghao Chong as a typical example. The results showcase how, through the meaningful application of historical knowledge, urban canals can become a water landscape infrastructure that effectively integrates public space by combining design, heritage, water management, and ecology.Landscape ArchitectureSpatial Planning and Strateg

Vehicle Dynamics Control Using Model Predictive Control Allocation Combined with an Adaptive Parameter Estimator

Advanced passenger vehicles are complex dynamic systems that are equipped with several actuators, possibly including differential braking, active steering, and semi-active or active suspensions. The simultaneous use of several actuators for integrated vehicle motion control has been a topic of great interest in literature. To facilitate this, a technique known as control allocation (CA) has been employed. CA is a technique that enables the coordination of various actuators of a system. One of the main challenges in the study of CA has been the representation of actuator dynamics in the optimal CA problem (OCAP). Using model predictive control allocation (MPCA), this problem has been addressed. Furthermore, the actual dynamics of actuators may vary over the lifespan of the system due to factors such as wear, lack of maintenance, etc. Therefore, it is further required to compensate for any mismatches between the actual actuator parameters and those used in the OCAP. This is done by combining the MPCA solver with an online adaptive parameter estimation (APE) algorithm. In this study, an advanced solution to the OCAP is proposed by combining MPCA with APE. This solution coordinates differential braking and active front steering (AFS) of a passenger vehicle, to stabilize the lateral and yaw motion. The simulation results indicate that the APE+MPCA combination effectively accounts for actuator dynamics and actuator parameter mismatches.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Intelligent Vehicle

Mitigating Motion Sickness with Optimization-Based Motion Planning

The acceptance of automated driving is under the potential threat of motion sickness. It hinders the passengers' willingness to perform secondary activities. In order to mitigate motion sickness in automated vehicles, we propose an optimization-based motion planning algorithm that minimizes the distribution of acceleration energy within the frequency range that is found to be the most nauseogenic. The algorithm is formulated into integral and receding-horizon variants and compared with a commonly used alternative approach aiming to minimize accelerations in general. The proposed approach can reduce frequency-weighted acceleration by up to 11.3% compared with not considering the frequency sensitivity for the price of reduced overall acceleration comfort. Our simulation studies also reveal a loss of performance by the receding-horizon approach over the integral approach when varying the preview time and nominal sampling time. The computation time of the receding-horizon planner is around or below the real-time threshold when using a longer sampling time but without causing significant performance loss. We also present the results of experiments conducted to measure the performance of human drivers on a public road section that the simulated scenario is actually based on. The proposed method can achieve a 19% improvement in general acceleration comfort or a 32% reduction in squared motion sickness dose value over the best-performing participant. The results demonstrate considerable potential for improving motion comfort and mitigating motion sickness using our approach in automated vehicles.Intelligent VehiclesTeam Tamas Keviczk

Reactivating Public Life through Water. Lessons from the Forgotten Historical Canals in Guangzhou

In the heart of the Pearl River Delta, the city of Guangzhou is fast-growing and prone to flooding. In history, people constructed canals based on natural waterways to deal with water problems. The canal system not only served as an important infrastructure but was also as the backbone of urban life. The city was built around its canals; they were the lifeline of Guangzhou. But with the development of the road network in recent decades, the urban canals in the historical inner city have been neglected and are disappearing, losing their identity, and becoming the forgotten side of the city. Also, canal restoration projects often only address the historical canals as water infrastructure, without effectively addressing them as public spaces. They are no longer designed as socially inclusive urban spaces and so play no significant role in public life anymore. Restoration projects are not really concerned with the canals or their surrounding urban tissue as a system, neither do they connect the lives of local people to the water. Therefore, the newly designed public spaces in these projects often function poorly, if at all. What can be learned from the historical situation to re-activate the urban canals as carriers of socially and ecologically inclusive urban space?Landscape ArchitectureSpatial Planning and Strateg