A sliding-mode grid voltage observer (SMGVO) is proposed and experimentally verified in this paper for voltage-sensorless operation under an unbalanced network. The fundamental positive sequence ...component (FPSC) and fundamental negative sequence component (FNSC) are inherently separated in the observer without employing any additional filters. Due to embedded filtering effect, high frequency chattering and harmonic ripples can be well suppressed. Additionally, dc components can be completely rejected. As a result, dc offset would not cause fundamental frequency oscillations in magnitude and frequency of the estimated FPSC and FNSC. Owing to the predictive ability of SMGVO, one-step delay can be directly compensated using state variables in the observer. By combining estimation and prediction into one stage, the designed SMGVO turns out to be a compact solution for finite-control-set model predictive power control without voltage sensors. Theoretical proof is derived to verify that FPSC and FNSC can be accurately estimated and separated. Experimental results obtained from a two-level PWM rectifier confirm the effectiveness of the whole control system.
Research and advancing understanding of the tumor immune microenvironment (TIME) is vital to optimize and direct more effective cancer immune therapy. Pre-clinical bench research is vital to better ...understand the genomic interplay of the TIME and immune therapy responsiveness. However, a vital key to effective translational cancer research is having a bridge of translation to bring that understanding from the bench to the bedside. Without that bridge, research into the TIME will lack an efficient and effective translation into the clinic and cancer treatment decision making. As a clinical oncologist, the purpose of this commentary is to emphasize the importance of researching and improving clinical utility of the bridge, as well as the TIME research itself.
•Single reduction, DCT and CVT based battery electric vehicle models are compared.•Shifting schedules for two-speed DCT and simplified CVT are optimized.•Up to 14% motor efficiency improvements and ...15% energy saving are achieved.•Improvement results in multi-speed BEVs are experimentally validated.•Initial manufacturing cost, lifetime daily use and maintenance cost are presented.
Despite the long-term benefit of battery electric vehicles (BEVs) to customers and environment, the initial cost and limited driving range present significant barriers for wide spread commercialization. The integration of multi-speed transmissions to BEVs’ powertrain systems in place of fixed ratio reduction transmissions is considered as a feasible method to improve powertrain efficiency and extend limited driving range for a fixed battery size. The aim of this paper is to enable the researchers or BEV manufacturers, especially for transmission systems, to estimate whether their products are worthwhile for the customer in terms of the price/performance relationship of others’ design solutions. To do so a generic battery electric vehicle is modelled in Matlab/Simulink® to predict motor efficiency and energy consumption for single reduction, two speeds Dual Clutch Transmission (DCT) and simplified Continuous Variable Transmission (CVT) equipped battery electric vehicles. A credible conclusion is gained, through experimental validation of single speed and two speeds DCT scenarios and reasonable assumptions to support the CVT scenario, that both two speeds DCT and simplified CVT improve the overall powertrain efficiency, save battery energy and reduce customer costs. However, each of the configurations has unique cost and energy consumption related trade-offs.
This paper presents a robust deadbeat predictive power control (DPPC) for pulsewidth modulation (PWM) rectifiers with the consideration of parameter mismatches under unbalanced grid conditions. ...First, conventional DPPC is modified to extend its application to both ideal and unbalanced grid conditions. Second, a tracking error of the modified DPPC with inaccurate grid-side impedance is analyzed. Third, a discrete-time power disturbance observer (DPDO) is designed to achieve accurate power control with mismatched parameters. The designed DPDO can predict complex power at the next sampling instant and estimate system disturbance simultaneously. Therefore, the DPDO can contribute to eliminate the steady-state tracking error resulting from disturbances caused by inaccurate parameters and compensate one-step delay in digital implementation. Although satisfactory steady-state performance can be obtained with modified DPPC and DPDO, transient performance still deteriorates significantly with an inaccurate value of the grid-side inductance. Thus, an online adaptive method to estimate mismatched inductance is finally developed based on the proposed DPDO. Both DPPC and DPDO are implemented in the stationary reference frame without coordinate transformation. Theoretical analysis confirms that the proposed DPDO can track disturbance without phase lag or magnitude error. Experimental tests and comparative studies with a prior DPPC on a two-level PWM rectifier validate the effectiveness of the proposed scheme.
Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of ...patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies.
Tumor-associated macrophage (TAM) phagocytic activity is emerging as a new mechanism to harness for cancer treatment. Currently, many approaches are investigated at the preclinical level and some ...modalities have now reached clinical trials, including the targeting of the phagocytosis inhibitor CD47. The rationale for increasing TAM phagocytic activity is to improve innate anticancer immunity, and to promote T-cell mediated adaptive immune responses. In this context, a clear understanding of the impact of TAM phagocytosis on both innate and adaptive immunity is critical. Indeed, uncertainties persist regarding the capacity of TAM to present tumor antigens to CD8 T cells by cross-presentation. This process is critical for an optimal cytotoxic T-cell immune response and can be mediated by dendritic cells but also potentially by macrophages. In addition, the engulfment of cancer cells affects TAM functionality, as apoptotic cell uptake (a process termed efferocytosis) promotes macrophage anti-inflammatory functions. Because of the abundance of TAM in most solid tumors and the common use of apoptosis inducers such as radiotherapy to treat patients with cancer, efferocytosis potentially affects the overall immune balance within the tumor microenvironment (TME). In this review, we will discuss how cancer cell phagocytosis by TAM impacts antitumor immunity. First, we will focus on the potential of the phagocytic activity of TAM per se to control tumor progression. Second, we will examine the potential of TAM to act as antigen presenting cells for tumor specific CD8 T cells, considering the different characteristics of this process in the tumor tissue and at the molecular level. Finally, we will see how phagocytosis and efferocytosis affect TAM functionality and how these mechanisms impact on antitumor immunity. A better understanding of these aspects will enable us to better predict and interpret the consequences of cancer therapies on the immune status of the TME. Future cancer treatment regimens can thereby be designed to not only impact directly on cancer cells, but also to favorably modulate TAM phagocytic activity to benefit from the potential of this central immune player to achieve more potent therapeutic efficacy.
•Electric vehicle equipped with dual motors and four-speed automated manual transmission.•Novel shift schedules and respective mode selection maps for accelerating and braking condition.•Hysteresis ...zones between upshift and downshift lines based on the equivalent motor efficiency.•Coordinated control of gear shift and mode transition.
The electric vehicle equipped with dual motors and four-speed automated manual transmission has demonstrated its superiority in improving energy efficiency and dynamic performance. To exploit this configuration effectively, optimal shift schedules and corresponding mode selection maps are proposed separately for accelerating and braking conditions. Hysteresis zones between upshift and downshift lines are created by properly integrating a priority factor into the equivalent motor efficiency. Interestingly, the proposed shift schedules depend not only on the motor efficiency map, motor torque allocation, but also on the current working gear pair. Besides, the intersections of the shift schedules and mode selection borders show that gear shift and mode transition need to be implemented at the same time. Therefore, a coordinated control strategy is developed to handle these requirements. Finally, simulation results show that the case of without hysteresis zones achieves minimum electricity consumption but with many undesired and unnecessary gear changes. Conversely, with comparable energy economy, the introduced priority factor of 0.02 avoids the shift hunting effectively. Moreover, taking the advantages of the powertrain configuration, the proposed coordinated control strategy eliminates all torque gaps under the gearshift and mode transition, so great shift quality is achieved.
As one of the deadliest diseases, cancer frequently resists existing therapeutics because they do not target all cells within a progressing tumor, for example both tumor stem and proliferating cells. ...This frequently results in enrichment of invasive and metastatic drug-resistant tumor cells subpopulations, cancer recurrence and eventually, patient mortality. Thus, there is an urgent need to identify specific markers, by which the targeted imaging and/or therapeutic “guided missile”-like agents can specifically detect and/or eradicate all cancer cells within a heterogeneous tumor, while leaving the normal cells intact. As a member of heat shock protein 70 (HSP70) superfamily, glucose regulated protein 78 (GRP78) has been documented as a molecular chaperone in the endoplasmic reticulum (ER) which mainly responds to ER stresses in normal cells. There is over-expression of GRP78 on the surface of cancer cells and angiogenic endothelial cells, which makes it a promising target for different types of peptides and antibodies that can be employed for targeted cancer therapy or imaging. In this review, we discuss the biological processes, functional importance and translocation mechanisms of cell surface GRP78 (csGRP78) in tumor cells. As a cancer biomarker, we also review the potential applications of csGRP78 targeted therapy and imaging and finally we suggest a brief roadmap ahead of csGRP78 targeting for targeted theranostic implications.
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•csGRP78 is expressed principally by cancer cells and angiogenic endothelial cells.•csGRP78 is a promising cancer biomarker and target for imaging and therapy.•csGRP78 targeting moieties can be integrated into nanoparticles.•Anti-csGRP78 antibodies targeting different epitopes differ in therapeutic impact.•New-generation csGRP78-targeting agents should encourage clinical testing.
Polymyxin B hemoperfusion reduces blood endotoxin levels in sepsis. Endotoxin activity can be measured in blood with a rapid assay. Treating patients with septic shock and elevated endotoxin activity ...using polymyxin B hemoperfusion may improve clinical outcomes.
To test whether adding polymyxin B hemoperfusion to conventional medical therapy improves survival compared with conventional therapy alone among patients with septic shock and high endotoxin activity.
Multicenter, randomized clinical trial involving 450 adult critically ill patients with septic shock and an endotoxin activity assay level of 0.60 or higher enrolled between September 2010 and June 2016 at 55 tertiary hospitals in North America. Last follow-up was June 2017.
Two polymyxin B hemoperfusion treatments (90-120 minutes) plus standard therapy completed within 24 hours of enrollment (n = 224 patients) or sham hemoperfusion plus standard therapy (n = 226 patients).
The primary outcome was mortality at 28 days among all patients randomized (all participants) and among patients randomized with a multiple organ dysfunction score (MODS) of more than 9.
Among 450 eligible enrolled patients (mean age, 59.8 years; 177 39.3% women; mean APACHE II score 29.4 range, 0-71 with higher scores indicating greater severity), 449 (99.8%) completed the study. Polymyxin B hemoperfusion was not associated with a significant difference in mortality at 28 days among all participants (treatment group, 84 of 223 37.7% vs sham group 78 of 226 34.5%; risk difference RD, 3.2%; 95% CI, -5.7% to 12.0%; relative risk RR, 1.09; 95% CI, 0.85-1.39; P = .49) or in the population with a MODS of more than 9 (treatment group, 65 of 146 44.5% vs sham, 65 of 148 43.9%; RD, 0.6%; 95% CI, -10.8% to 11.9%; RR, 1.01; 95% CI, 0.78-1.31; P = .92). Overall, 264 serious adverse events were reported (65.1% treatment group vs 57.3% sham group). The most frequent serious adverse events were worsening of sepsis (10.8% treatment group vs 9.1% sham group) and worsening of septic shock (6.6% treatment group vs 7.7% sham group).
Among patients with septic shock and high endotoxin activity, polymyxin B hemoperfusion treatment plus conventional medical therapy compared with sham treatment plus conventional medical therapy did not reduce mortality at 28 days.
ClinicalTrials.gov Identifier: NCT01046669.
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