Let there be oxygen and T cells Walker, Paul R
The Journal of clinical investigation,
11/2018, Letnik:
128, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The stroma of solid tumors can exclude or limit immune infiltration, or lead to the recruitment of tumor-promoting rather than tumor-attacking immune cells. This finding was reported by Jayaprakash ...et al. in this issue of the JCI, and it was particularly prominent in the hypoxic zones of tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer models. A current clinical goal of immune checkpoint blockade (ICB) is to extend its utility to more patients by converting immunologically "cold" tumors that do not provoke a strong immunological response to "hot" tumors that are invaded by swarms of T cells. When the underlying cause is hypoxia linked, the therapeutic combination of simultaneous targeting of hypoxia and immune checkpoints merits exploration in future clinical trials.
What are normal relaxation times of tissues at 3 T? Bojorquez, Jorge Zavala; Bricq, Stéphanie; Acquitter, Clement ...
Magnetic resonance imaging,
January 2017, 2017-Jan, 2017-01-00, 20170101, Letnik:
35
Journal Article
Recenzirano
The T1 and T2 relaxation times are the basic parameters behind magnetic resonance imaging. The accurate knowledge of the T1 and T2 values of tissues allows to perform quantitative imaging and to ...develop and optimize magnetic resonance sequences. A vast extent of methods and sequences has been developed to calculate the T1 and T2 relaxation times of different tissues in diverse centers. Surprisingly, a wide range of values has been reported for similar tissues (e.g. T1 of white matter from 699 to 1735ms and T2 of fat from 41 to 371ms), and the true values that represent each specific tissue are still unclear, which have deterred their common use in clinical diagnostic imaging. This article presents a comprehensive review of the reported relaxation times in the literature in vivo at 3T for a large span of tissues. It gives a detailed analysis of the different methods and sequences used to calculate the relaxation times, and it explains the reasons of the spread of reported relaxation times values in the literature.
To achieve the best possible responses during shifting in dual clutch transmissions it is commonplace to integrate clutch and engine control, while the clutch is used to match speeds between the ...engine and wheels via reduction gears, poor engine control can lead to extended engagement times and rough/harsh shift transients. This paper proposes a method for combined speed and torque control of vehicle powertrains with dual clutch transmissions for both the engine and clutches. The vehicle powertrain is modelled as a simple four degree of freedom system with reduction gears and two clutches. Including a detailed clutch hydraulic model, comprising of the direct acting solenoids and clutch piston with the hydraulic fluid modelled as a compressible fluid. Powertrain control is realised through control of clutch solenoids and manipulation of the engine throttle input. Sensitivity study of clutch performance evaluating inaccurate torque estimation demonstrated variance in the response of the hydraulic system, with an indicative simulation of poor estimation resulting in increased powertrain vibration during and after shifting. Simulations are conducted to demonstrate the capacity for this method of engine and clutch control to further reduce shift transients developed in dual clutch transmission powertrains. The obtained results also show that the adoption of torque based control techniques for both the clutch and engine, which makes use of the estimated target clutch torque, significantly improves the powertrain response as a result of reduction in the lockup discontinuities.
The modern energy management strategy (EMS) plays a vital role in the energy efficiency of the extended range electric vehicle. However, some modern strategies such as model predictive control (MPC) ...and dynamic programming (DP) have limited practical potential because they are subject to the pre-known environment information and noise interference. The reinforcement learning (RL)control strategy can be adopted as online control to interact with the vehicle and the environment. In this study, a novel auxiliary power unit (APU) charging strategy with multi-object optimization is proposed to achieve high fuel conversion efficiency while maintaining battery charging health. The state-of-the-art algorithm, Soft Actor-Critic (SAC), is applied to achieve better exploration of the possible APU behaviour and solve the sensitivity and poor convergence problems from the current RL studies. Its performance is further verified by the results of the Deep Deterministic Policy Gradient (DDPG) algorithm and DP. Three innovative targets are selected as the RL rewards for optimization: the engine fuel rate, SOC charging trajectory, and the battery charging rate (C-rate). The first adoption of the battery C-rate monitoring in RL-based energy management strategy helps extend the battery lifespan from excessive discharge. The comparative results show that the SAC had a 36% faster convergence speed than DDPG while providing a smoother and more stable action space. The fuel consumption with SAC also outplays that of DDPG by around 3%, which achieves almost 95% of the global optimization result. The successful deployment of the SAC algorithm as an EMS indicates its standout ability in dealing with wide-range actions and states with high randomness, revealing the practical potential compared with the existing RL strategies.
•A deep RL-based charging control strategy with maximum entropy is proposed.•A reward constraint of the battery C-rate is considered for battery protection.•Engine power and engine RPM are the multi-actions for a stabilized control.
•Development of a multispeed dual input clutchless transmission system.•Achieve non-interrupted power-on shifting with the proposed shifting control strategy.•A real-time PSC strategy is designed to ...both improve efficiency and drivability.•Simulations demonstrate the effectiveness of proposed system and its control strategies.
To improve the overall efficiency of electric vehicles and guarantee the driving comfort and vehicle drivability under the concept of simplifying mechanism complexity and minimizing manufacturing cost, this paper proposes a novel clutchless power-shifting transmission system with shifting control strategy and power sharing control strategy. The proposed shifting strategy takes advantage of the transmission architecture to achieve power-on shifting, which greatly improves the driving comfort compared with conventional automated manual transmission, with a bump function based shifting control method. To maximize the overall efficiency, a real-time power sharing control strategy is designed to solve the power distribution problem between the two motors. Detailed mathematical model is built to verify the effectiveness of the proposed methods. The results demonstrate the proposed strategies considerably improve the overall efficiency while achieve non-interrupted power-on shifting and maintain the vehicle jerk during shifting under an acceptable threshold.
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•Limited permeability of BBB and BBTB makes glioma treatment a troublesome challenge.•Liposomes are considered among the most widely used NPs for glioma treatment.•Side effects as the ...results of off-targeting are minimized by actively targeted liposomes.•Liposomal active targeting is a promising tool for future advanced brain cancer therapy.
High-grade glioma is one of the most aggressive types of cancer with a low survival rate ranging from 12 to 15 months after the first diagnosis. Though being the most common strategy for glioma therapy, conventional chemotherapy suffers providing the therapeutic dosage of common therapeutics mostly because of limited permeability of blood–brain barrier (BBB), and blood–brain tumor barrier (BBTB) to anticancer agents. Among various nanoformulations, liposomes are considered as the most popular carriers aimed for glioma therapy. However, non-targeted liposomes which passively accumulate in most of the cancer tissues mainly through the enhanced permeation and retention effect (EPR), may not be applicable for glioma therapy due to BBB tight junctions. In the recent decade, the surface modification of liposomes with different active targeting ligands has shown promising results by getting different chemotherapeutics across the BBB and BBTB and leading them into the glioma cells. The present review discusses the major barriers for drug delivery systems to glioma, elaborates the existing mechanisms for liposomes to traverse across the BBB, and explores the main strategies for incorporation of targeting ligands onto the liposomes. It subsequently investigates the most recent and relevant studies of actively targeted liposomes modified with antibodies, aptamers, monosaccharides, polysaccharides, proteins, and peptides applied for effective glioma therapy, and highlights the common challenges facing this area. Finally, the actively targeted liposomes undergoing preclinical and clinical studies for delivery of different anticancer agents to glioma cells will be reviewed.
This paper proposes a new real-time energy management strategy (R-EMS) to improve the fuel economy performance of the power-split hybrid electric vehicles (HEVs). Being different from most ...conventional optimization-based EMS, the R-EMS does not need priori information of the driving cycle and is used to the online control of HEV. The forward dynamic model of power-split powertrain is built based on the Prius MY10. At each instant, the proposed R-EMS tries to minimize the equivalent consumed power of the HEV, which is the weighted summation of gasoline power and battery output power. The equivalence factor of battery output power has a clear physical meaning that is the efficiency of gasoline energy transferred to battery energy. Another two coefficients are introduced to control the state of charge (SOC) of battery. By considering the engine torque and engine speed as two independent or dependent design variables, respectively, the 2-D R-EMS and 1-D R-EMS are formed. Several typical driving cycles are used to simulate the performance of the R-EMS, and the results show that the proposed R-EMS not only maintains the battery SOC but also saves the fuel consumption compared with the rule-based EMS.
Extracellular vesicle (EV) secretion is a ubiquitous cellular process with both physiologic and pathologic consequences. EVs are small lipid bilayer vesicles that encompass both microvesicles and ...exosomes and which are secreted by virtually all cells including cancer cells. In this review, we will focus on the roles of EVs in mediating the crosstalk between glioblastoma (GBM) cells and innate and adaptive immune cells and the potential impact on glioma progression. Glioma-derived EVs contain many bioactive cargoes that can broaden and amplify glioma cell mediated immunosuppressive functions and thereby contribute to shaping the tumor microenvironment. We will discuss evidence demonstrating that the low oxygen (hypoxia) in the GBM microenvironment, in addition to cell-intrinsic effects, can affect intercellular communication through EV release, raising the possibility that properties of the tumor core can more widely impact the tumor microenvironment. Recent advances in glioma-derived EV research have shown their importance not only as message carriers, but also as mediators of immune escape, with the capacity to reprogram tumor infiltrating immune cells. Exploring EV function in cancer-immune crosstalk is therefore becoming an important research area, opening up opportunities to develop EV monitoring for mechanistic studies as well as novel diagnostic glioma biomarker applications. However, robust and reproducible EV analysis is not always routinely established, whether in research or in clinical settings. Taking into account the current state of the art in EV studies, we will discuss the challenges and opportunities for extending the many exciting findings in basic research to a better interpretation of glioma and its response to current and future immunotherapies.
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