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Preeclampsia (PE) is a condition that poses a significant risk of maternal mortality and multiple organ failure during pregnancy. Early prediction of PE can enable timely surveillance and interventions, such as low-dose aspirin administration. In this study, conducted at Stanford Health Care, we examined a cohort of 60 pregnant women and collected 478 urine samples between gestational weeks 8 and 20 for comprehensive metabolomic profiling. By employing liquid chromatography mass spectrometry (LCMS/MS), we identified the structures of seven out of 26 metabolomics biomarkers detected. Utilizing the XGBoost algorithm, we developed a predictive model based on these seven metabolomics biomarkers to identify individuals at risk of developing PE. The performance of the model was evaluated using 10-fold cross-validation, yielding an area under the receiver operating characteristic curve of 0.856. Our findings suggest that measuring urinary metabolomics biomarkers offers a noninvasive approach to assess the risk of PE prior to its onset. [ABSTRACT FROM AUTHOR]

Objective: Twins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twins. This study reports the performance of an SNP‐based NIPT in the largest cohort with known outcomes for high‐risk aneuploidy results. Method: This is a retrospective analysis of 18,984 results from commercial single‐nucleotide polymorphism (SNP)‐based NIPT tests performed in twins between October 2, 2017 and December 31, 2019. Follow‐up for all 211 high‐risk cases was solicited. Results: Follow‐up outcomes were obtained in 105 cases. Positive predictive values (PPVs) for high‐risk results were 88.7% (63/71, 95% Confidence Interval [CI]: 79.0%–95.0%) for trisomy 21% and 72.7% (8/11, 95% CI: 39.0%–94.0%) for trisomy 18. The results were stratified into monozygotic (MZ) and dizygotic (DZ). The PPVs in MZ were 100% for both trisomy 21 (4/4, 95% CI: 40%–100%) and trisomy 18 (1/1, 95% CI: 2.5%–100%). No trisomy 13 cases were detected in the MZ group. The PPVs in DZ were 88.1% (59/67, 95% CI: 77.8%–94.7%), 70.0% (7/10, 95% CI: 34.8%–93.3%), and 66.7% (2/3, 95% CI: 9.4%–99.2%) for trisomy 21, trisomy 18, and trisomy 13, respectively. Conclusion: The performance of SNP‐based NIPT in this large twin cohort was comparable to previously reported twin NIPT studies. SNP‐based NIPT allows for zygosity‐based PPV assessment. Key points: What is already known about this topic? Limited clinical experience has been published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twin pregnancies, despite twins accounting for about 1 in 30 live births in the United States.SNP‐based NIPT provides both zygosity and the individual fetal fractions in dizygotics during prenatal aneuploidy screening in twin pregnancies. What does this study add? This study based on a large cohort of twin pregnancies reports positive predictive values (PPVs) for detecting common aneuploidies in pregnancies identified as high‐risk‐using SNP‐based NIPT.This is the first study to evaluate the PPV in DZ and MZ twins using NIPT. [ABSTRACT FROM AUTHOR]

In order to improve the performance of motor drive systems, this paper introduces a sensorless control method for interior permanent magnet synchronous motors (IPMSM) based on the rotating high-frequency voltage injection method. The demodulation method using a synchronous frequency filter (SFF) instead of a bandpass filter (BPF) and a high pass filter (HPF) is proposed. The structure and transfer function of SFFs are introduced, and their characteristics are simulated and analyzed. Therefore, the center frequency of SFFs can be adaptively adjusted according to the estimated rotational speed, which is convenient for frequency setting. Finally, according to the proposed rotating high-frequency voltage injection method, the simulation model is built. The experimental results verify that the control strategy can maintain good position estimation accuracy, better speed tracking performance and anti-load disturbance performance. [ABSTRACT FROM AUTHOR]

In this article, to improve the accuracy of rotor position estimation in sensorless permanent magnet synchronous motor drives, a reduced-order resonant regulator for the rotor position sliding mode observer is proposed. Since fundamental back electromotive force can be utilized to calculate the rotor position, a mathematical model for the observer is first established based on the analysis of estimation fluctuation error, where a reduced-order resonant regulator is applied to extract the fundamental back electromotive force. Then, the phase-locked loop with back electromotive force normalization is used to compute the rotor position and speed. Finally, the experimental bench of permanent magnet synchronous motor driving system is built. The experimental results verify that the proposed strategy can effectively reduce the estimation error and meanwhile improve estimation accuracy. [ABSTRACT FROM AUTHOR]

The flux-concentrating permanent-magnet (FCPM) machine with two V-shape magnet pieces in one stator pole has attracted considerable attention due to its excellent torque density and permanent magnet (PM) usage efficiency, whereas the torque ripple of the FCPM machine is usually high. This article aims to make a multiobjective optimization design for the FCPM machine. The optimization process is divided into three steps for different optimization objectives on two sets of geometric variables at different operation conditions. The simulated results show that the output torque of the optimized FCPM machine is increased significantly while the torque ripple has been decreased greatly. Finally, the open-circuit field distributions, the output torque, the torque-speed characteristics, and PM demagnetization of the optimized FCPM machine are investigated considering different PM shapes and PM temperature rise, which indicates that the optimized FCPM machine has favorable torque characteristics, speed range, and antidemagnetization abilities. [ABSTRACT FROM AUTHOR]

Background: Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms. Methods: Serum levels of placenta-related proteins–leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)–were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice. Results: An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs. Conclusions: Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model. [ABSTRACT FROM AUTHOR]

A fast and precise lumped-parameter thermal network (LPTN) model is presented for a flux-switching permanent-magnet double-rotor machine used for hybrid electric vehicles (HEVs), which has attracted attention due to the compact structure. The three-dimensional (3-D) LPTN model provides the steady-state thermal solution to derive the temperatures at different parts of the machine, in which the power losses of various working conditions are used as heat sources for calculating the temperatures of different operational modes. In the LPTN studies, a transformation of an irregular slot structure into a regular one is applied to simplify the calculation of the winding thermal resistance. A 3-D finite element thermal model of this machine is also established to calculate the temperatures of the main machine components for a comparative study purpose. Tests performed on the designed machine verify that the defined LPTN model has a high ability to predict the nodal temperatures accurately. [ABSTRACT FROM AUTHOR]

In this paper, an outer-rotor-permanent-magnet flux-switching (ORPM-FS) machine is proposed. It not only inherits the traditional flux-switching permanent-magnets (FSPM's) flux-switching principle and the high torque density, but also overcomes the FSPM's magnetic saturation and adds the slot area, thus producing favorable output torque capability at rated load and overload condition. By means of finite element method, the ORPM-FS machine is optimized through multi-level process for multi-objectives: the basic variables optimization for high output torque and low torque ripple, the pitch coefficient optimization for favorable torque characteristics and efficiency, the optimal selection for high efficiency at flux-weakening operation. At last, the electromagnetic performances of the optimized ORPM-FS machine are analyzed, which shows that the proposed machine can receive high torque density, low torque ripple, high efficiency, and favorable overload capability. [ABSTRACT FROM AUTHOR]

In order to reduce the axial length and increase the critical speed of the small magnetic suspension drive system, a new slice hybrid magnetic bearing (SHMB) with two radial air-gaps is proposed. The structure and suspension mechanism of the SHMB is introduced, and then the mathematical models of the radial suspension force are deduced using the equivalent magnetic circuit method. The suspension mechanism is proved. The radial and axial suspension forces are then calculated by the finite element method. The experimental prototype SHMB is finally designed and constructed. The stable suspension of the rotor is realized, and the suspension forces are measured. The results of the finite element calculation and experimental measurement verify the correctness of the mathematical models. [ABSTRACT FROM AUTHOR]

The multimechanical-port double-rotor machine, as a core component in hybrid electric vehicles, has attracted considerable attention due to the merits of compact structure, control flexibility, and diverse performances. However, since there often exist two electric or mechanical ports in one compound machine frame, traditional design theory cannot be applied to it directly. Besides, because of the relatively complex machine structure and multiple design parameters, design objectives often influence even conflict with each other. In this paper, a new multiobjective optimization design approach is proposed to design and optimize a flux-modulated double-rotor flux-switching permanent magnet machine, where multiple driving modes are considered. To verify the feasibility of the double-rotor machine and the effectiveness of an optimization design method, the electromagnetic characteristics of the machine are investigated in detail. Finally, a prototype machine is built and tested. Both theoretical analysis and experimental results verify the validity of the proposed machine and multiobjective optimization design approach. [ABSTRACT FROM AUTHOR]

The flux-switching permanent-magnet (PM) double-rotor machine (FSPM-DRM) used for hybrid electric vehicles has attracted considerable attention due to the compact structure and high torque density. Compared with the conventional machine, the FSPM-DRM suffers from more iron loss, PM eddy-current loss, and conductor eddy-current loss for its larger rotor pole numbers. The iron loss exists not only in the stator but also in the rotor, while its calculation becomes more difficult due to complex flux density waveforms. A more accurate analytical model for the iron loss, PM eddy-current loss, and conductor eddy-current loss calculation is proposed for the FSPM-DRM and compared with the results from finite-element method. Based on the calculated losses, the efficiency of the FSPM-DRM is also investigated. Some experimental results are reported, validating the numerical and simulation results. [ABSTRACT FROM AUTHOR]

The flux-switching permanent-magnet double-rotor machine (FSPM-DRM) used for hybrid electric vehicles has attracted considerable attention due to the compact structure and high torque density. Compared with conventional machine, the FSPM-DRM suffers from more severe thermal problems in its inner rotor. This paper aims to make an accurate prediction of the performances and temperature distributions in the FSPM-DRM. First, the eddy current loss in windings with an improved analytical method is discussed and the results are validated by those from a 2-D finite-element (FE) model. With the obtained power losses, the lumped-parameter scheme considering end effect is compared with a 3-D FE thermal model to predict the temperature in each part of the FSPM-DRM at hybrid driving mode, in which both yield similar results. Then the maximum temperatures of different parts at the rated load and 160% load under various operational modes are simulated. Some experimental results are reported, validating the numerical and simulated results. [ABSTRACT FROM AUTHOR]

The traditional bearingless permanent magnet synchronous motor has complex decoupling control problems. To overcome the drawbacks above, a novel hybrid permanent magnet type bearingless motor (HPMTBM) is proposed in this paper, which has integrated the merits of hybrid excitation permanent magnet motor and magnetic bearings. The main advantages of this HPMTBM are the simple control mechanism and the low power consumption. First, the principle and theoretical background of this motor are introduced. Then, the mathematical models of radial suspension force and torque are established using Maxwell stress tensor method, and air-gap magnetic fields, radial suspension forces are calculated by finite-element analysis. Finally, the prototype motor is designed and constructed. The radial suspension forces and rotor radial displacements are tested. The simulation and experimental results show the feasibility of the proposed HPMTBM. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites-driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance. [ABSTRACT FROM AUTHOR]

The use of double-rotor machines (DRMs) for hybrid electric vehicles (HEVs) has attracted considerable attention due to their compact structure and high torque density. Compared with the conventional four-quadrant transducer (4QT), the proposed flux switching permanent magnet double-rotor machine (FSPM-DRM) has PMs located in the stator, and can offer better performances in terms of magnetic coupling and torque ripple, which are especially important for DRM control in HEVs. This paper presents a comparative analysis of the 4QT and FSPM-DRM by employing the finite element method (FEM). For a fair comparison, two topologies are designed under the same peripheral dimensions, current density, and copper loss. Considering the effect of skewed slots in the 4QT, the corresponding performances are calculated with multi-slice 2-D time-stepping FEM. The simulated results illustrate that the proposed FSPM-DRM offers larger output torque, lower torque ripple, and smaller magnetic coupling than the 4QT. Nevertheless, the eddy current losses in PMs and windings of the FSPM-DRM are higher than those of the 4QT. Experimental results of the FSPM-DRM prototype are also given to verify the validity. [ABSTRACT FROM AUTHOR]

This paper presents the comparison of linear primary permanent magnet vernier (LPPMV) machine and linear vernier hybrid (LVH) machine. The LPPMV machine and the LVH machine both operate based on the magnetic gear principle, hence possessing the advantages of low speed and high thrust force density. In addition, both machines employ similar configurations between which the key difference is that a one-piece primary iron core is employed in the LPPMV machine instead of the modular cores in the LVH machine. Using the finite element method (FEM), the characteristics and performances of two machines are analyzed and compared. The results show that the LPPMV machine exhibits higher thrust force and lower cogging force. Finally, the FEM results are validated by experiments based on a prototype of the LPPMV machine. [ABSTRACT FROM AUTHOR]

In the permanent magnet (PM) machines, the Halbach PM (HPM) machine can offer higher performance than others, while they require more rare-earth PMs. Due to the high price of rare-earth PMs, such as NdFeB and SmCo magnets, the cost has become a serious drawback of the HPM machine. To overcome this disadvantage, a new fault-tolerant HPM (FTHPM) machine by mixing rare-earth PM and ferrite magnets is proposed in this paper. The proposed machine can be a good candidate for many applications because of low price and stable supply of ferrite magnets. Furthermore, the lumped parameter magnetic circuit method is used to analyze the proposed FTHPM machine. In addition, the finite element method is adopted to verify the effectiveness of the theoretical analysis. [ABSTRACT FROM AUTHOR]

This paper proposes a new magnetic planetary geared permanent magnet brushless (MPG-PMBL) machine for hybrid electric vehicles. According to the dynamic performances in hybrid electric vehicles, the proposed machine needs to offer the advantages of high power density, high efficiency, and low torque ripple. To realize these goals, a multi-objective optimization design method based on the combined design of experiments approach and response surface method is presented, where three key optimization objectives of the efficiency, total loss, and cogging torque are selected. After the optimization, some reasonable key design variables are determined and the proposed MPG-PMBL machine is newly designed and built for evaluation. Both theoretical analysis and experimental results verify the validity of the proposed optimization method. [ABSTRACT FROM AUTHOR]

This paper proposes a new linear hybrid excited flux reversal motor with inset permanent magnets (PMs). The proposed motor adopts the excitation windings in the primary, hence offering the desired flux control capability. The novelty of the proposed motor is to design a modular primary structure. Then, it has very symmetrical and sinusoidal back electromotive force (back-EMF) and smooth thrust even at various excitation currents. In addition, because of the inset PMs, the proposed motor is free from PM irreversible demagnetization. The electromagnetic performances of the proposed motor are analyzed using the time-stepping finite-element method, such as magnetic field distribution, back-EMF, and thrust, verifying the effectiveness of the theoretical analysis. [ABSTRACT FROM AUTHOR]

This paper proposes an axial permanent magnet-biased hybrid magnetic bearing, which possesses the advantages of low power consumption, simple structure, and easy control. The structure and operation principle are introduced. Then, the mathematical models, including the suspension force expression, are built based on traditional equivalent magnetic circuit. In addition, the basic principle of structure parameter design is presented, based on which the key parameters are given. Due to the inaccuracy of the traditional equivalent magnetic circuit, an improved method for magnetic circuit is introduced. Last, the accuracy of the analytical method is validated by finite element analysis and it also has an important reference value for other types of magnetic bearings design. [ABSTRACT FROM AUTHOR]

Endophytic bacteria are generally helpful for plant growth and protection. Strain WSE01, which was identified as bacillus cereus , was isolated from the stem of Myriophyllum verticillatum and it displayed a high tolerance to Mn (1500 mg/L). The strain was found to be able to produce indole-3-acetic acid (IAA) and siderophores, fix the atmospheric nitrogen and dissolve potassium from insoluble K-bearing minerals. In hydroponic culture experiments, the inoculation of strain WSE01 significantly promoted the growth and increased the leaf enzyme activity in the inoculated plant M. verticillatum. Furthermore, the manganese content was increased by 36.4% in stems and by 54.7% in leaves of the inoculated plant under Mn stress at 400 mg/L, compared to the non-inoculated group. This study suggests that the strain WSE01 has the potential to be used as biocontrol and/or biofertilizing agents for application in macrophyte M. verticillatum and conduces to achieving more effective phytoremediation of metal-contaminated waters. Unlabelled Image • An endophytic strain WSE01 isolated from M. verticillatum displays high tolerance to Mn. • Strain WSE01 was identified as bacillus cereus and it has plant growth promotion traits. • Inoculation of strain WSE01 promotes the plant growth with and without Mn stress. • Strain WSE01 enhances manganese accumulation in its host plant M. verticillatum. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation., Study Design: Retrospective discovery and longitudinal confirmation., Setting: Maternity units from two US hospitals., Participants: Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation., Outcome Measures: Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays., Results: Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation., Conclusions: Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this study was to develop a single blood test that could determine gestational age and estimate the risk of preterm birth by measuring serum metabolites. We hypothesised that serial metabolic modelling of serum analytes throughout pregnancy could be used to describe fetal gestational age and project preterm birth with a high degree of precision., Study Design: A retrospective cohort study., Setting: Two medical centres from the USA., Participants: Thirty-six patients (20 full-term, 16 preterm) enrolled at Stanford University were used to develop gestational age and preterm birth risk algorithms, 22 patients (9 full-term, 13 preterm) enrolled at the University of Alabama were used to validate the algorithms., Outcome Measures: Maternal blood was collected serially throughout pregnancy. Metabolic datasets were generated using mass spectrometry., Results: A model to determine gestational age was developed (R 2 =0.98) and validated (R 2 =0.81). 66.7% of the estimates fell within ±1 week of ultrasound results during model validation. Significant disruptions from full-term pregnancy metabolic patterns were observed in preterm pregnancies (R 2 =-0.68). A separate algorithm to predict preterm birth was developed using a set of 10 metabolic pathways that resulted in an area under the curve of 0.96 and 0.92, a sensitivity of 0.88 and 0.86, and a specificity of 0.96 and 0.92 during development and validation testing, respectively., Conclusions: In this study, metabolic profiling was used to develop and test a model for determining gestational age during full-term pregnancy progression, and to determine risk of preterm birth. With additional patient validation studies, these algorithms may be used to identify at-risk pregnancies prompting alterations in clinical care, and to gain biological insights into the pathophysiology of preterm birth. Metabolic pathway-based pregnancy modelling is a novel modality for investigation and clinical application development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lead halide perovskites with good optoelectronic properties and high attenuation of high-energy radiation are great candidates for X-ray radiation detectors. Large area, dense, and thick films or wafers are a prerequisite for these applications. In this paper, a one-step heat-assisted high-pressure press method is developed to directly prepare a large (the largest has a diameter of 80 mm) and thickness- and shape-controlled phase-pure organic-inorganic hybrid CH 3 NH 3 PbI 3 wafer of densely packed large microcrystals from raw powder materials. Meanwhile, this method uses no solvent to achieve essentially 100% material utilization. The obtained wafers show good ambipolar carrier mobilities of ∼20 cm 2 V -1 s -1 and a μτ product as high as 3.84 × 10 -4 cm 2 V -1 . Under an X-ray source using an acceleration voltage of 40 kV, the perovskite wafer-based X-ray detector shows an X-ray sensitivity as large as 1.22 × 10 5 μC Gy air -1 cm -2 under a 10 V bias, the highest reported for any perovskite material. The method provides a convenient strategy for producing large perovskite wafers with good optoelectronic properties, which will facilitate the development of large perovskite devices.

The occurrence of emerging pollutants (EPs) is continuously reported worldwide. Nevertheless, only few of these compounds are toxicologically evaluated due to their vast numbers. Reliable analytical methods and toxicity assessment methods are the basis of either the management or the elimination of EPs. In this paper, literature published in 2018 on EPs were reviewed with special regard to their occurrence, detection methods, fate in the environment, and ecological toxicity assessment. Particular focus was placed on practical considerations, novel processes, and new solution strategies. PRACTITIONER POINTS: Literature published in 2018 on emerging pollutants were reviewed. This review article is with special regard to the occurrence, detection methods, fate and toxicity assessment of emerging pollutants. Particular focus was placed on practical considerations, novel processes and new solution strategies., (© 2019 Water Environment Federation.)

Patients with ovarian cancer are generally diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common. The volume of ascites correlates positively with the extent of metastasis and negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic reticulum chaperone that is also expressed on the plasma membrane ((mem)GRP78) of aggressive cancer cells, plays a crucial role in the embryonic stem cell maintenance. We studied the effects of ascites on ovarian cancer stem-like cells using a syngeneic mouse model. Our study demonstrates that ascites-derived tumor cells from mice injected intraperitoneally with murine ovarian cancer cells (ID8) express increased (mem)GRP78 levels compared with ID8 cells from normal culture. We hypothesized that these ascites-associated (mem)GRP78(+) cells are cancer stem-like cells (CSC). Supporting this hypothesis, we show that (mem)GRP78(+) cells isolated from murine ascites exhibit increased sphere forming and tumor initiating abilities compared with (mem)GRP78(-) cells. When the tumor microenvironment is recapitulated by adding ascites fluid to cell culture, ID8 cells express more (mem)GRP78 and increased self-renewing ability compared with those cultured in medium alone. Moreover, compared with their counterparts cultured in normal medium, ID8 cells cultured in ascites, or isolated from ascites, show increased stem cell marker expression. Antibodies directed against the carboxy-terminal domain of GRP78: (i) reduce self-renewing ability of murine and human ovarian cancer cells preincubated with ascites and (ii) suppress a GSK3α-AKT/SNAI1 signaling axis in these cells. Based on these data, we suggest that (mem)GRP78 is a logical therapeutic target for late-stage ovarian cancer., (©2015 American Association for Cancer Research.)

A correlation between expression of the glucose-regulated protein of 78 kDa (GRP78) in malignant melanoma tumors and poor patient survival is well established. In this study, in addition to demonstrating the expression of GRP78 in tumor tissue, we investigated the immune response against GRP78 in a group of patients with different progression stages of malignant melanoma. Furthermore, we analyzed the glycosylation status of GRP78 immunoglobulin (Ig) G autoantibodies at these stages and evaluated their capacities to affect the protein B-dependent protein kinase signaling pathway and unfolded protein response signaling mechanisms, all known to promote malignant melanoma cell proliferation and survival. We found that progression of disease correlates not only with enhanced expression of GRP78 in the tumor but also with an increase in GRP78 autoantibody serum titers in these patients. We also found that the glycosylation status of anti-GRP78 IgG changes as the disease progresses. The anti-GRP78 IgG is abnormally glycosylated in the Fc region and asymmetrically glycosylated in the Fab region. We demonstrate that hyperglycosylated anti-GRP78 IgGs stimulate cell proliferation through protein B-dependent protein kinase signaling pathways. They also mimic the effects of α2-macroglobulin on the upregulation of GRP78 and X-box binding protein 1, activating transcription factor 6 α, and serine/threonine-protein kinase/endoribonuclease precursor α as endoplasmic reticulum stress biomarkers and show no effect on expression or activation of caspases 3, 9, or 12. In conclusion, the anti-GRP78 IgG autoantibodies downregulate apoptosis and activate unfolded protein response mechanisms, which are essential to promote melanoma cell growth and survival.