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Many solid tumors, including ovarian cancer, contain small populations of cancer stem cells (CSCs). These cells are usually resistant against conventional cancer therapies and play a role in disease recurrence. We demonstrated that the L1 cell adhesion molecule (L1CAM) is a new CSC target in ovarian cancer, triggering radioresistance. Using fluorescence-activated cell sorting, specific cell populations expressing L1CAM alone or in combination with the established CSC marker CD133 were isolated from three ovarian cancer cell lines. Double-positive L1CAM+/CD133+ cells displayed higher spherogenic and clonogenic properties in comparison to L1CAM−/CD133− cells. Furthermore, L1CAM+/CD133+ cells retained highest clonogenic capacity after irradiation and exhibited up-regulation of some CSC-specific genes, enhanced tumor-initiating capacity, self-renewal and higher tumor take rate in nude mice when compared with other cell populations. Superior radioresistance by L1CAM expression was confirmed by deletion of L1CAM using CRISPR-Cas9 technology. Moreover, we found expression signatures associated with epithelial-to-mesenchymal transition phenotype in L1CAM deleted cells. These results indicate that L1CAM in combination with CD133 defines a new cancer cell population of ovarian tumor-initiating cells with the implication of targeting L1CAM as a novel therapeutic approach for ovarian CSCs., Cancers, 12 (1), ISSN:2072-6694

Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient’s outcome. Identification of the molecular players involved in ovarian cancer dissemination can offer an approach to develop treatment strategies to improve clinical prognosis. Here, we identified mesothelin (MSLN) as a crucial protein in the multistep process of peritoneal dissemination of ovarian cancer. We demonstrated that MSLN is overexpressed in primary and matched peritoneal metastasis of high-grade serous carcinomas (HGSC). Using several genetically engineered ovarian cancer cell lines, resulting in loss or gain of function, we found that MSLN increased cell survival in suspension and invasion of tumor cells through the mesothelial cell layer in vitro. Intraperitoneal xenografts established with MSLNhigh ovarian cancer cell lines showed enhanced tumor burden and spread within the peritoneal cavity. These findings provide strong evidences that MSLN is a key player in ovarian cancer progression by triggering peritoneal dissemination and provide support for further clinical investigation of MSLN as a therapeutic target in HGSC. This work was partly developed at IPATIMUP, an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and I3S. This work was supported by FEDER–Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This research was funded by projects PTDC/MEC-ONC/29503/ 2017 (to L.D.), NORTE 2020 grant numbers NORTE-01-0145-FEDER-000029, NORTE-01-0145-FEDER-000003, Wilhelm Sander Stiftung 2018.010.1 (to F.J.), Swiss Cancer League KLS-3841-02-2016 (to F.J.), and FCT PhD fellowship number SFRH/BD/111885/2015 (to R.C.) We would like to thank Dr. Ronny Drapkin (University of Pennsylvania) for sharing the fallopian tube cell lines.

600 mV magneto-electric switching in 30 nm La-doped BiFeO 3 multiferroic oxide and a proof of concept 7 μV spin-orbit signal output in Pt / CoFe local spin injection device with 100 μA supply current were experimentally demonstrated at room temperature for the 1st time. Also demonstrated was a path towards 70 mV spin orbit output using Bi 2 Se 3 in a local spin injection device. These are key accomplishments for WRITE and READ building blocks, respectively, toward realization of a magneto-electric spin-orbit (MESO) energy-efficient logic device. Moreover, the 1st generation of a MESO logic device with a functional READ unit is demonstrated.

The competition between order parameters, such as ferroelectricity, ferromagnetism, and superconductivity, is one of the most fascinating topics in condensed matter physics. Here, we report intriguing anisotropic superconductivity in YBa2Cu3O7 − x films induced by a multiferroic, BiFeO3, with periodic domain patterns. The anisotropic superconductivity was investigated by transport measurements and supported by phase-field simulations, and then the detailed local electronic structures were revealed by cross-sectional scanning tunneling microscopy. We found that the oxygen redistribution in YBa2Cu3O7 − x modulated by the ferroelectric polarization in BiFeO3 was the key mechanism driving this anisotropic superconductivity. The presented heteroarchitecture of a high-temperature superconductor and a domain-engineered multiferroic provides a new approach to tune superconductivity and offers potential advantages for the design of future multifunctional devices. Combining two unusual materials offers a way to fine-tune superconductivity, according to scientists in Taiwan, China and the USA. Multiferroics are both ferromagnetic—that is, they become permanently magnetised when exposed to a magnetic field—and ferroelectric, the electric equivalent of ferromagnetism. This combination allows the electric control of magnetism. Ying-Hao Chu from the National Chiao Tung University in Hsinchu City, Taiwan, and co-workers have shown that multiferroics can also control superconductivity. The team combined thin films of the multiferroic bismuth ferrite (BiFeO3) and a superconductor called YBCO (YBa2Cu3O7-x). They found that the different ferroelectric areas in the bismuth ferrite caused a redistribution of the oxygen atoms in the YBCO, and this created a more exotic superconductor known as an asymmetric superconductor. This ability to tune superconductivity could be harnessed in future magnetoelectric devices. The periodic domain pattern of BiFeO3 enables the anisotropic superconductivity in YBa2Cu3O7 − x. In this work, we introduce a design of periodic multiferroic domain patterns to create the anisotropic superconductivity. High TC can be found when we measured the resistance parallel to the domain wall direction and the broader transition with lower TC is found to be perpendicular to the domain walls. (a) and (b) the resistance versus temperature in YBa2Cu3O7 − x/BiFeO3 heterostructures with two different domain patterns 109° and 71°, respectively.

Silver-based bonding wires such as Ag-4Pd and Ag-8Au-3Pd have drawn remarkable attention in the packaging industry because they are cheaper and more conductive than Au- and Cu-based wires, respectively. This study aimed to investigate the intermetallic compound (IMC) formation and growth at the bonding interface between Ag-4Pd wire and Al-pads and between Ag-8Au-3Pd wire and Al-pads. The as-bonded and reliability-tested Ag-4Pd/Al and Ag-8Au-3Pd/Al specimens were then investigated by transmission electron microscopy (TEM) and scanning transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy (STEM-EDS). The bonding properties were examined by ball shear and wire pull tests. In the as-bonded state, hexagonal close-packed (HCP) (Ag, Pd)2Al and HCP Ag2Al were formed at the Ag-4Pd/Al interfaces, whereas dual phase consisting of face-centered cubic Ag alloy with HCP precipitates (Ag, Au, Pd)2Al crystals and HCP Ag2Al layers were observed at the Ag-8Au-3Pd/Al interfaces. The IMCs showed significant growth and oxidation during reliability tests at 130 °C and 85 pct relative humidity for 192 hours. Alloying Au in Ag-4Pd wires promoted the growth of the IMC layer and it also enhanced the mechanical properties in the as-bonded material. By contrast, overgrowth of the IMCs in the Ag-8Au-3Pd/Al system induced microcrack formation in bonding and thus degraded the reliability of the material.

The reversible transitions of cancer cells between epithelial and mesenchymal states comprise cellular and molecular processes essential for local tumor growth and respective dissemination. We report here that globoside glycosphingolipid (GSL) glycosyltransferase-encoding genes are elevated in epithelial cells and correlate with characteristic EMT signatures predictive of disease outcome. Depletion of globosides through CRISPR-Cas9–mediated deletion of the key enzyme A4GALT induces EMT, enhances chemoresistance, and increased CD24low/CD44high cells. The cholera toxin–induced mesenchymal-to-epithelial transition occurred only in cells with functional A4GALT. Cells undergoing EMT lost E-cadherin expression through epigenetic silencing at the promoter region of CDH1. However, in ΔA4GALT cells, demethylation was able to rescue E-cadherin–mediated cell–cell adhesion only in the presence of exogenous A4GALT. Overall, our data suggest another class of biomolecules vital for epithelial cancer cells and for maintaining cell integrity and function. Significance: This study highlights the essential role of glycosphingolipids in the maintenance of epithelial cancer cell properties. Cancer Res; 78(11); 2952–65. ©2018 AACR.

Spin–orbit torque (SOT) magnetoresistive random-access memory (MRAM) devices have been proposed for energy efficient memory and computing applications. New classes of materials such as antiferromagnets, topological insulators, and semimetals can generate spins with unconventional polarization and improve the efficiency of field-free SOT switching. In this work, we report significant changes in SOTs due to a Co thin film inserted in the Pt/Co/Mg/CoFeB heterostructures. Remarkably, the damping-like effective field has been enhanced by 7.4 times after inserting a thin Co layer with weak perpendicular magnetic anisotropy (PMA), while the field-like effective field is reduced to near zero value. Independent characterizations were performed to verify the presence of the changes in SOTs following spin modulation by the Co insertion layer. In addition, we found that the dynamic spin pumping coupling between Pt/Co with weak PMA and the in-plane CoFeB could significantly modulate the effective SOTs in the heterostructure, and this effect is dependent on the thickness of the spacer Mg through long-range spin-wave mediated coupling. Our work has experimentally demonstrated a new avenue to modulate SOTs with physically sputtered metal layers, and this finding is promising to enable flexible and efficient spin polarizations for MRAM devices.

La1−xSrxMnO3 (LSMO) is well known as an efficient spin-injection electrode in ferromagnetic–organic hybrid-based organic spin valves (OSV). Herein, we examine the influence of three terminating layers of LSMO films (mixed-, MnO2-, and LaSrO- (LSO-) terminated) on the spin filter at the bottom interface of tri (8-hydroxyquinoline) aluminum (Alq3) deposited on these substrates. Angle-dependent X-ray photoelectron spectra (XPS) demonstrated the presence of SrO segregation at the outermost layer for three types of LSMO films but in different amounts that might contribute to their magnetic properties. A weak surface coupling between LSMO and Alq3 was obtained through a small increase of Mn L-edge X-ray magnetic circular dichroism (XMCD) but it does not vary the bulk magnetic properties of LSMO films upon Alq3 adsorption (LSMO/Alq3). The surface dipoles due to the interaction between LSMO films and Alq3 were found to be 0.5, 0.5, and 0.7 eV for the mixed-ter/Alq3, MnO2-ter/Alq3, and LSO-ter/Alq3 interfaces, respectively. Our results indicate that the segregated SrO layer plays an important role in the surface electronic and magnetic properties at LSMO/Alq3 interfaces, which contributes to a fundamental understanding of the spin injection and transport in LSMO-Alq3 hybrid-based OSV devices.

We have studied low-energy configurations in two-dimensional arrays consisting of Ising-type dipolar coupled nanomagnets lithographically defined onto a two-dimensional Cairo lattice, thus dubbed the dipolar Cairo lattice. Employing synchrotron-based photoemission electron microscopy (PEEM), we perform real-space imaging of moment configurations achieved after thermal annealing. These states are then characterized in terms of vertex populations, spin- and emergent magnetic charge correlations, and a topology-enforced emergent ice rule. The results reveal a strong dominance of short-range correlations and the absence of long-range order, reflecting the high degree of geometrical spin frustration present in this example of an artificial frustrated spin system.

Purpose Sentinel lymph node biopsy (SLNB) is the standard management for clinically node-negative cutaneous melanoma patients. This study aimed to evaluate the role of SLNB in Taiwanese melanoma patients and in particular, patients with acral lentiginous melanoma (ALM). Patients and methods We retrospectively analyzed the clinicopathological characteristics and survival outcomes of the patients who underwent primary surgery followed by either SLNB or nodal observation at the Linkou Chang Gung Memorial Hospital from January 2000 to December 2011. Results Among the total of 209 patients, 127 underwent SLNB and 51 underwent nodal observation only after primary surgery. There were no significant differences in clinicopathological features between the two groups except that patients who underwent SLNB were older and had a higher rate of ALM than those under nodal observation. The median follow-up time was 43.5 months until July 2013. The patients who underwent SLNB had significantly better disease-free survival (DFS) (57.1 vs 18.7 months, p < 0.01) and melanoma-specific survival (MSS) (112.4 vs 45.2 months, p < 0.01) than those under observation. Improvement in DFS (HR: 0.51, p < 0.01) and MSS (HR: 0.60, p = 0.03) was observed even after adjusting for age and disease pathology by multivariate analysis. This benefit of clinical outcomes persisted in patients with ALM, Breslow thickness ≤2 mm, or no ulceration, but not in patients with non-ALM, Breslow thickness >2 mm, or ulceration. Conclusion SLNB was associated with favorable outcomes in patients with clinically node-negative cutaneous melanoma, particularly in Taiwanese patients with ALM, Breslow thickness ≤2 mm, and nonulcerated melanoma.

Nanoelectronic devices based on ferroelectric domain walls (DWs), such as memories, transistors, and rectifiers, have been demonstrated in recent years. Practical high-speed electronics, on the other hand, usually demand operation frequencies in the gigahertz (GHz) regime, where the effect of dipolar oscillation is important. Herein, an unexpected giant GHz conductivity on the order of 10

Background/purpose: Pulmonary veno-occlusive disease (PVOD) is a rare but fatal cause of pulmonary hypertension reported to be linked to mutations of eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4), also known as general control nonderepressible 2 kinase (GCN2). PVOD is difficult to diagnose and often initially misdiagnosed as other types of idiopathic pulmonary arterial hypertension (IPAH). To rapidly and correctly identify PVOD patients and explore the possible pathogenesis, we thoroughly investigated histopathological features and GCN2 protein levels in non-PAH, PVOD and PAH patients. Methods: Lung specimens were examined for histopathological changes, including those of pulmonary arteries and veins, by Masson's trichrome, modified Verhoeff's and α-SMA staining in the PVOD, IPAH, and non-PAH groups. GCN2 and α-SMA expression in lung tissue was examined by immunohistochemistry and western blotting. Results: PVOD and IPAH patients showed significant intimal and medial thickening of muscular pulmonary arteries compared with non-PAH patients. PVOD patients had more prominent intimal and medial thickening of muscular pulmonary veins than the other two groups. Interestingly, specialized muscle bundles surrounding the tunica adventitia of the pulmonary artery and vein were observed in PVOD patients. A significant decrease in GCN2 expression in the PVOD group was confirmed by immunohistochemistry and western blotting. Conclusion: Our study is the first to show remarkable histological structures, including the wreath-like arrangement of a hyperplastic muscle bundle in the adventitia of pulmonary arteries, in PVOD patients as a diagnostic clue and to disclose the biological difference between PAH and PVOD in a Taiwanese population. Keywords: Pulmonary veno-occlusive disease, Histopathological features, Hyperplastic muscle bundle

6024 Background: Epidermal growth factor receptor (EGFR) pathway inhibition may synergize with anti-PD1 activity by inhibiting macrophage function, increasing antigen presentation, and augmenting T cell responses. Afatinib, an irreversible EGFR tyrosine kinase inhibitor (TKI), has been shown to enhance anti-PD1 activity in in vitro and animal studies. We thus hypothesized that adding afatinib to pembrolizumab may improve the treatment outcomes for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Methods: The ALPHA study (NCT03695510) is a single-arm, phase II study with a Simon 2-stage design. Patients with platinum-refractory, recurrent, or metastatic HNSCC are eligible for the study. Afatinib (40mg, oral, daily) and pembrolizumab (200mg, every 3 weeks) are administered to eligible patients. The primary endpoint is the objective response rate (ORR). PD-L1 IHC testing (22C3), comprehensive genomic profiling (CGP, Roche Foundation Medicine One CDx), and targeted multiplexed gene expression profiling (Nanostring nCounter PanCancer Immune Profiling Panel) were applied for biomarker analysis. Results: From JAN 2019 to MAR 2020, 29 patients were enrolled in the study. Age: mean = 53.4 years old; M/F = 27/2. Tumor type: oral cavity: 19; oropharynx: 6, hypopharynx: 2, larynx: 2. PD-L1 TPS > = 50: 7/29 (24.1%), CPS > = 20: 8/29 (27.6%), TMB > 10: 0/25 (0%). The common treatment-related adverse events (AEs; all grades, grade > = 3) were skin rash (22/29, 4/29), diarrhea (17/29, 3/29), paronychia (13/29, 0/29), mucositis (9/29, 1/29), and weight loss (2/29, 0/29). One patient experienced grade 2 pneumonitis. Twelve patients had partial responses to the treatment (12/29, ORR: 41.4%). The data cut-off date was 11FEB2021. The median progression free survival (PFS) was 4.1 (95% confidence interval [CI], 1.9-6.3) months. The median overall survival (OS) was 8.4 (95% CI, 4.1-10.8) months. Patients with high PD-L1 expression had a higher response rate (TPS > = 50: ORR = 0.71, CPS > = 20: ORR = 0.63). EGFR amplification might also predict a higher response rate (ORR: 3/3, 100%). MTAP loss or mutation may predict a poor response to the treatment (ORR: 0/5, 0%), shorter PFS (HR: 4.21, [95% CI: 1.34-13.24], p = 0.014), and shorter OS (HR: 4.20 [95% CI: 1.32-13.41], p = 0.015). Nine patients underwent paired pre-treatment and post-treatment biopsies for gene expression analysis. The mRNA of HLA-A, HLA-B, CXCL13, CXCL9, and CD8A were elevated in the post-treatment biopsies. Three patients underwent post-progression biopsies for CGP study. One patient had a new MTAP mutation. Conclusions: Afatinib can modify tumor microenvironment and increase the clinical response rate in pembrolizumab-based therapy in HNSCC patients. PD-L1, EGFR amplification, and MTAP loss/mutation could be biomarkers for cancer immunotherapy. Clinical trial information: NCT03695510.

Dislocations in ferroelectrics play important roles in ferroelectricity, piezoelectricity, and dielectricity. However, the intrinsic charge-lattice coupling mechanism in ferroelectric crystals containing dislocations is still not well understood. Here, we report a large local polarization inhomogeneity of ~100 μCcm−2 induced by a single a[001] dislocation in the PbZr0.2Ti0.8O3/SrTiO3 film/substrate heterostructure, the tensile region (~120 μCcm−2) and the compressive strain region (~21 μCcm−2) around the dislocation forms a butterfly-like area. This study reveals the dramatic effects of dislocations on local polarization and provides a strategy to manipulate the polarization magnitude and orientation of local polarization by defect engineering.

Introduction: Kras mutation is the most common driver oncogene present in patients with NSCLC. Recently, the precision medicine for patients with Kras-mutated NSCLC has been under investigation, but the best treatment is still unknown. This study aimed to analyze the clinical characteristics, immune checkpoint inhibitor (ICI) response, and prognostic factors of patients with NSCLC with different Kras mutation subtypes. Methods: From 2005 to 2018, we collected nonsquamous NSCLC tissue samples for Kras mutation analysis using direct Sanger sequencing or MassARRAY genotyping (Agena Bioscience, San Diego, CA) at the National Taiwan University Hospital. Clinical characteristics, ICI treatment effectiveness, time-to-tumor recurrence (TTR), and overall survival (OS) were analyzed using multivariate Cox models, to estimate adjusted hazard ratios (HRs). Results: Among 5278 patients with nonsquamous NSCLC, 246 (4.7%) had Kras mutations. The major Kras mutation subtypes were G12C (32.9%), G12D (23.7%), and G12V (18.9%). Patients with Kras-G12C had a higher proportion of male individuals (p = 0.018) and smokers (p < 0.001). Among the 25 patients treated with ICIs, patients with Kras-G12C had a higher response rate (53.8% versus 8.3%, p = 0.030) and longer progression-free survival (4.8 mo versus 2.1 mo, p = 0.028) than those with Kras-non-G12C. For the 85 patients with early-stage NSCLC, those with G12C had shorter TTR (22.8 mo) than those with Kras-non-G12C (97.7 mo, p = 0.004). For the 143 patients with advanced-stage NSCLC, there was a significant difference in OS between patients with Kras-G12C and Kras-non-G12C (7.7 mo versus 6.0 mo, p = 0.018) and patients with Kras-G12V had the shortest OS (5.2 mo). Multivariate analysis revealed association of shorter OS with Kras-G12V (HR = 2.47, p = 0.002), stage IV disease status (HR = 2.69, p = 0.008), and NSCLC—not otherwise specified histology (HR = 3.12, p = 0.002). Conclusions: Kras-G12C was associated with favorable ICI treatment effectiveness in patients with NSCLC. Kras-G12C mutation was associated with shorter TTR in patients with early-stage NSCLC, and Kras-G12V mutation was associated with shorter OS in patients with advanced-stage NSCLC when comparing with Kras-G12C.

237 Background: Previous studies have indicated B cells as potential predictive markers for anti-PD-1 blockade therapy in several cancer types. The study explored whether B cells in TME and B cell related gene signatures are associated with clinical benefit (CB) for ESCC patients receiving anti-PD-1/PD-ligand 1 (PD-L1) therapy. Methods: Sixty-six ESCC patients treated with PD-1/PD-L1 blockade-based immunotherapy were enrolled. Tumor response was evaluated per RECIST 1.1, and CB was defined as complete response, partial response or stable disease at least 6 months. Transcriptome of formalin-fixed paraffin-embedded ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel (n=25), Gene Set Enrichment Analysis (GSEA) was performed to identify the differential immune-related pathways, and CIBERSORT was applied to estimate the levels of infiltrating immune cells. The expression of CD20 was evaluated by immunohistochemistry (IHC) (n=66). Results: Of 66 enrolled patients (M: F= 65: 1, median age of 59), 44 and 22 were of recurrent and de novo metastatic ESCC. Forty and 26 received PD-1/PD-L1 blockade alone and PD-1/PD-L1-based combination immunotherapy, respectively. The response rate was 17%, and the CB rate was 24%. The median progression-free-survival (PFS) and overall survival are 1.8 and 5.5 months, respectively. B cell signature was significantly increased in patients with CB ( P < 0.05) and associated with longer progression-free survival and overall survival (both P < 0.05). The genes related to B cells, B cell functions, and T cell functions were up-regulated in patients with CB compared to that with non-CB (all P < 0.05). Naïve B cells and plasma cells were significantly increased in patients with CB (both P < 0.05). The expression levels of stromal CD20 by IHC trended to increase in patients with CB ( P = 0.08). Conclusions: B cells in tumor microenvironment may be associated with CB of anti-PD-1/PD-L1 therapy in patients with ESCC. (Funded by MOST 105-2314-B-002 -186 -MY3; MOHW107-TDU-B-211-114017; MOST 108-2314-B-002 -076 -MY3; MOST 107-2314-B-002-199 -).

Every living cell is covered with a dense and complex layer of glycans on the cell surface, which have important functions in the interaction between cells and their environment. Glycosphingolipids (GSLs) are glycans linked to lipid molecules that together with sphingolipids, sterols, and proteins form plasma membrane lipid rafts that contribute to membrane integrity and provide specific recognition sites. GSLs are subdivided into three major series (globo-, ganglio-, and neolacto-series) and are synthesized in a non-template driven process by enzymes localized in the ER and Golgi apparatus. Altered glycosylation of lipids are known to be involved in tumor development and metastasis. Metastasis is frequently linked with reversible epithelial-to-mesenchymal transition (EMT), a process involved in tumor progression, and the formation of new distant metastatic sites (mesenchymal-to-epithelial transition or MET). On a single cell basis, cancer cells lose their epithelial features to gain mesenchymal characteristics via mechanisms influenced by the composition of the GSLs on the cell surface. Here, we summarize the literature on GSLs in the context of reversible and cancer-associated EMT and discuss how the modification of GSLs at the cell surface may promote this process.

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studiedin vitroand adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.

The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii–Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3., The coupling of ferroelectric and antiferromagnetic order in BiFeO3 makes it appealing for applications however the presence of domain structure acts to undermine this potential. Here, the authors demonstrate BiFeO3 thin films with a single domain of electrical polarization and canted antiferromagnetic order.

Ferroelectric photoelectrodes, other than conventional semiconductors, are alternative photo-absorbers in the process of water splitting. However, the capture of photons and efficient transfer of photo-excited carriers remain as two critical issues in ferroelectric photoelectrodes. In this work, we overcome the aforementioned issues by decorating the ferroelectric BiFeO3 (BFO) surface with Au nanocrystals, and thus improving the photoelectrochemical (PEC) performance of BFO film. We demonstrate that the internal field induced by the spontaneous polarization of BFO can (1) tune the efficiency of the photo-excited carriers' separation and charge transfer characteristics in bare BFO photoelectrodes, and (2) modulate an extra optical absorption within the visible light region, created by the surface plasmon resonance excitation of Au nanocrystals to capture more photons in the Au/BFO heterostructure. This study provides key insights for understanding the tunable features of PEC performance, composed of the heterostructure of noble metals and ferroelectric materials.

Nanoelectronic devices based on ferroelectric domain walls (DWs), such as memories, transistors, and rectifiers, have been demonstrated in recent years. Practical high-speed electronics, on the other hand, usually demand operation frequencies in the gigahertz (GHz) regime, where the effect of dipolar oscillation is important. Herein, an unexpected giant GHz conductivity on the order of 103 S m-1 is observed in certain BiFeO3 DWs, which is about 100 000 times greater than the carrier-induced direct current (dc) conductivity of the same walls. Surprisingly, the nominal configuration of the DWs precludes the alternating current (ac) conduction under an excitation electric field perpendicular to the surface. Theoretical analysis shows that the inclined DWs are stressed asymmetrically near the film surface, whereas the vertical walls in a control sample are not. The resultant imbalanced polarization profile can then couple to the out-of-plane microwave fields and induce power dissipation, which is confirmed by the phase-field modeling. Since the contributions from mobile-carrier conduction and bound-charge oscillation to the ac conductivity are equivalent in a microwave circuit, the research on local structural dynamics may open a new avenue to implement DW nano-devices for radio-frequency applications.

Neurofibromatosis type 1 (NF1) is a germline autosomal dominant disorder caused by the loss-of-function tumor suppressor gene NF1, which encodes neurofibromin protein. When multiple tumors arise within a short time in patients with the germline NF1 mutation, it is important to determine whether the tumors are metastatic or different primary tumors. We, herein, report a 35-year-old female with multiple tumors that were confirmed to be a malignant peripheral nerve sheath tumor, gastrointestinal stromal tumor, renal cell carcinoma, and pancreatic neuroendocrine tumor, and all were treated accordingly. This case further supports that tissue confirmation is important in patients with the NF1 germline mutation.

Magnetoelectricity enables a new class of nonvolatile, ultralow-energy computing with quantum materials for AI & Moore’s law., Demonstration of ultralow energy switching mechanisms is imperative for continued improvements in computing devices. Ferroelectric (FE) and multiferroic (MF) order and their manipulation promise an ideal combination of state variables to reach attojoule range for logic and memory (i.e., ~30× lower switching energy than nanoelectronics). In BiFeO3 (BFO), the coupling between the antiferromagnetic (AFM) and FE order is robust at room temperature, scalable in voltage, stabilized by the FE order, and can be integrated into a fabrication process for a beyond-CMOS (complementary metal-oxide semiconductor) era. The presence of the AFM order and a canted magnetic moment in this system causes exchange interaction with a ferromagnet such as Co0.9Fe0.1 or La0.7Sr0.3MnO3. Previous research has shown that exchange coupling (uniaxial anisotropy) can be controlled with an electric field. However, voltage modulation of unidirectional anisotropy, which is preferred for logic and memory technologies, has not yet been demonstrated. Here, we present evidence for electric field control of exchange bias of laterally scaled spin valves that is exchange coupled to BFO at room temperature. We show that the exchange bias in this bilayer is robust, electrically controlled, and reversible. We anticipate that magnetoelectricity at these scaled dimensions provides a powerful pathway for computing beyond modern nanoelectronics by enabling a new class of nonvolatile, ultralow energy computing elements.

Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO3 and EuTiO3. Despite this critical need, there are few studies on the strain evolution of magnetic order in BiFeO3 films. Here, in (110)-oriented BiFeO3 films, we reveal that while the polarization structure remains relatively unaffected, strain can continuously tune the orientation of the antiferromagnetic-spin axis across a wide angular space, resulting in an unexpected deviation of the classical perpendicular relationship between the antiferromagnetic axis and the polarization. Calculations suggest that this evolution arises from a competition between the Dzyaloshinskii–Moriya interaction and single-ion anisotropy wherein the former dominates at small strains and the two are comparable at large strains. Finally, strong coupling between the BiFeO3 and the ferromagnet Co0.9Fe0.1 exists such that the magnetic anisotropy of the ferromagnet can be effectively controlled by engineering the orientation of the antiferromagnetic-spin axis.

Pulmonary peripheral-type squamous cell carcinoma (p-SqCC) has been increasing in incidence. However, little is known about the clinicopathologic features of p-SqCC. This study aimed to investigate the clinicopathologic characteristics and clinical outcomes of p-SqCC compared with central-type SqCC (c-SqCC) in a large cohort of surgically resected lung SqCC patients with long-term follow-up results. The study included 268 patients with SqCC who underwent surgical resection at the authors’ institute from January 1990 to September 2013. The mean follow-up period was 67.1 months. The clinicopathologic and genetic characteristics were investigated in relation to their association with progression-free survival (PFS) and overall survival (OS) based on tumor location. The study cohort included 120 patients with p-SqCC and 148 patients with c-SqCC. Compared with c-SqCC, p-SqCC was correlated with older age (p = 0.002), female sex (p = 0.033), better performance status (p

Mixed squamous cell and glandular papilloma (mixed papilloma) is a very rare tumor, with fewer than 25 cases having been reported in the literature. Although a scattering of cases of p16

Controlling ferroic orders (ferroelectricity, ferromagnetism and ferroelasticity) by optical methods is a significant challenge due to the large mismatch in energy scales between the order parameter coupling strengths and the incident photons. Here, we demonstrate an approach to manipulate multiple ferroic orders in an epitaxial mixed-phase BiFeO

The effective screening of the polarization bound charge is a prerequisite to stabilize the ferroelectricity in ferroelectric thin films. Here, by combining annular bright field imaging and electron energy-loss spectroscopy (EELS) in an aberration-corrected scanning transmission electron microscope with phase-field simulations, we investigate the screening mechanism by quantitatively measuring the structural relaxation at $\mathrm{Pb}(\mathrm{Z}{\mathrm{r}}_{0.2}\mathrm{T}{\mathrm{i}}_{0.8}){\mathrm{O}}_{3}/\mathrm{SrTi}{\mathrm{O}}_{3}$ interfaces. We find that the thickness of the interfacial layer is $\ensuremath{\sim}3.5$ unit cells ($\ensuremath{\sim}1.4$ nm) in a domain with upward polarization and $\ensuremath{\sim}5.5$ unit cells ($\ensuremath{\sim}2.2$ nm) in a domain with downward polarization. Phase-field simulations, an EELS analysis, and a lattice parameter analysis verify the existence of interfacial oxygen vacancies accounting for the narrower interfacial layer in the domain with upward polarization. Our study indicates the internal structural relaxation at the interface is the dominant mechanism for the polarization charge screening for ferroelectric films grown on insulating substrates and has implications for our understanding of domain switching in ferroelectric devices.

The electrical generation and detection of elastic waves are the foundation for acoustoelectronic and acoustooptic systems. For surface acoustic wave devices, microelectromechanical/nanoelectromechanical systems, and phononic crystals, tailoring the spatial variation of material properties such as piezoelectric and elastic tensors may bring significant improvements to the system performance. Due to the much slower speed of sound than speed of light in solids, it is desirable to study various electroacoustic behaviors at the mesoscopic length scale. In this work, we demonstrate the interferometric imaging of electromechanical power transduction in ferroelectric lithium niobate domain structures by microwave impedance microscopy. In sharp contrast to the traditional standing-wave patterns caused by the superposition of counterpropagating waves, the constructive and destructive fringes in microwave dissipation images exhibit an intriguing one-wavelength periodicity. We show that such unusual interference patterns, which are fundamentally different from the acoustic displacement fields, stem from the nonlocal interaction between electric fields and elastic waves. The results are corroborated by numerical simulations taking into account the sign reversal of piezoelectric tensor in oppositely polarized domains. Our work paves ways to probe nanoscale electroacoustic phenomena in complex structures by near-field electromagnetic imaging.

Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO

To compare the frequency of microbleeds identified by susceptibility-weighted MRI (SWMRI) in patients with mild traumatic brain injury (mTBI) and normal controls, and correlate these findings with neuropsychological tests.Research ethics committee approval and patient written informed consents were obtained. One hundred eleven patients with mTBI without parenchymal hemorrhage on CT and conventional MRI received SWMRI as well as a digit span and continuous performance test. One hundred eleven healthy volunteers without history of traumatic brain injury were enrolled as the control group and received conventional MRI with additional SWMRI study. We analyzed the number and location of microbleeds in both groups.Twenty-six patients with mTBI and 12 control subjects presented microbleeds on SWMRI (p = 0.0197). Sixty microbleeds were found in 26 patients with mTBI and 15 microbleeds in 12 control subjects. The mTBI group showed notably more microbleeds in the cortex/subcortical region (52 microbleeds, 86.7%, vs 3 microbleeds, 20%; p0.0001). Conversely, the control group showed more microbleeds in the central brain (9 microbleeds, 60%, vs 3 microbleeds, 5%; p0.0001). There was no statistical difference in number of microbleeds in the cerebellum and brainstem (p = 0.2598 and p = 0.4932, respectively). Patients with mTBI who had detected microbleeds had lower digit span scores than the patients with negative SWMRI findings (p = 0.017).Presence of mTBI-related microbleeds showed a neuropsychological defect on short-term memory function, indicating that the presence of microbleeds could be a possible severity biomarker for mTBI. Addition of the SWMRI technique to the MRI protocol for patients with mTBI is recommended.

An annealing twinned Ag–4Pd binary alloy wire has been produced as an alternate material for a previously developed Ag–8Au–3Pd ternary alloy wire to meet requirements for high electrical conductivity and low cost. The electrical resistivity of this annealing twinned Ag-alloy bonding wire decreased drastically from the original value of 3.5 μΩ cm to about 2.9 μΩ cm after aging at 600 °C for 30 min. The decrease in electrical resistivity became moderate with longer aging times. In contrast to the apparent increase in grain size in a conventional Ag–4Pd wire during aging at 600 °C for various times, the grains in this annealing twinned wire grew much more slowly. The breaking load and elongation of this annealing twinned Ag–4Pd wire are also higher than those of conventional wire. The conventional grained Ag–4Pd wire has a slightly higher electrical resistivity of 3.7 μΩ cm than that of annealing twinned wire. However, the more rapid grain growth in the conventional grained Ag–4Pd wire led to a lower electrical resistivity than that of annealing twinned wire during aging process.

Although the size effect in ferroelectric thin films has been known for long time, the underlying mechanism is not yet fully understood and whether or not there is a critical thickness below which the ferroelectricity vanishes is still under debate. Here, we directly measure the thickness-dependent polarization in ultrathin PbZr0.2Ti0.8O3 films via quantitative annular bright field imaging. We find that the polarization is significantly suppressed for films, Understanding ferroelectricity at reduced dimensions will be important for future sub-nanoscale devices based on ferroelectrics. Using high resolution electron microscopy; Gao et al., observe the existence of a measurable polarization at a thickness of just 1.5-unit cells

The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR-Cas9 -mediated gene disruption of B3GNT5 (∆B3GNT5) on the expression of glycosphingolipids and N-glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling. ∆B3GNT5 cells lost nsGSL expression coinciding with reduction of α2-6 sialylation on N-glycoproteins. In contrast, disruption of B4GALNT1, a glycosyltransferase for ganglio series GSLs did not affect α2-6 sialylation on N-glycoproteins. We further profiled all known α2-6 sialyltransferase-encoding genes and showed that the loss of α2-6 sialylation is due to silencing of ST6GAL1 expression in ∆B3GNT5 cells. These results demonstrate that nsGSLs are part of a complex network affecting N-glycosylation in ovarian cancer cells.

The effects of Mn 3 O 4 addition and annealing under a reducing atmosphere (N 2 :H 2 =97:3) on the microstructure and phase stability of calcia-stabilized zirconia (CSZ) ceramics sintered at 1500 °C for 3 h in air were investigated. Undoped and Mn 3 O 4 -doped 12.5 mol% CSZ (125CSZ) ceramics were prepared via a conventional solid-state reaction process. X-ray diffraction patterns showed a single cubic phase of ZrO 2 in 0.3 mol% Mn 3 O 4 -doped 125CSZ after sintering at 1500 °C for 3 h. Monoclinic ZrO 2 phases were observed in 0.5 mol% Mn 3 O 4 -doped 125CSZ and undoped 15 mol% CSZ ceramic after annealing at 1300 °C for 30 cycles in a reducing atmosphere. The amount of monoclinic ZrO 2 phase observed in 0.5 mol% Mn 3 O 4 -doped 125CSZ was less than that found in undoped 15 mol% CSZ annealed at 1300 °C under a reducing atmosphere.

Introduction Integrins are glycosylated transmembrane receptor family proteins, mediate cancer cell to extracellular matrix (ECM) interaction. Integrins are essential for adhesion and migration of cancer cells and frequently associate with poor disease outcome. In addition, glycosylation of integrins modulates receptor and ligand binding affinity. However, the physiological role of glycosylation of integrins remain unclear. Based on our recent findings that disruption of glycosphingolipids triggering loss of α2,6-sialylation Alam et al. 2017 here, we identified integrin α2 as candidate and investigated its potential role in facilitating ovarian cancer metastasis. Material and methods Hypersialylated proteins were identified by lectin-enrichment proteomic analysis. CRISPR- Cas9 mediated site-specific deletion of integrin α2 together with a lentiviral-mediated rescue system were established in four ovarian cancer cell lines (IGROV1, SKOV3, SKOV3ip, and OVCAR4). ECM- and mesothelial cell- adhesion assays were applied to evaluate integrin-mediated in vitro cell adhesion, while a zebrafish transplant model was used to study in vivo cell invasion ability. Finally, integrin expression and sialylation profile were determined in patient-derived matched primary and metastatic ovarian cancer tumour specimens. Results and discussions Proteomic analysis identified integrin α2 as a hypersialylated protein in ovarian cancer cells. Loss of sialylation on N -glycoproteins of cancer cells reduced cell adhesion to collagen type I, fibronectin, and laminin. Furthermore, integrin α2 knockout cancer cells abolished cell adhesion to collagen whereas rescuing integrin α2 expression in those knockout cells fully restored the adhesion ability. We also identified an elevated level of intergin α2 in patient-derived metastatic tumour compared to primary site and tumor-free omentum, indicating a niche for ovarian cancer cells toward omental metastasis. Conclusion Our data demonstrate that α2,6 sialylation on integrin α2 triggers ovarian cancer cell adhesion to metastatic sites. Therefore, blocking sialylation and integrin α2 may be a therapeutic target for preventing ovarian cancer metastasis in the future.

The effects of Mn3O4 addition and reductive atmosphere (N2:H2 = 97:3) annealing on the microstructure and phase stability of yttria stabilized zirconia (YSZ) ceramics during sintering at 1500 °C for 3 h in air and subsequent annealing in a reductive atmosphere were investigated. Mn3O4 added 6 mol% YSZ (6YSZ) and 10 mol% YSZ (10YSZ) ceramics were prepared via the conventional solid-state reaction processes. The X-ray diffraction results showed that a single cubic phase of ZrO2 was obtained in 1 mol% Mn3O4 added 6YSZ ceramic at a sintering temperature of 1500 °C for 3 h. A trace amount of monoclinic ZrO2 phases were observed for 1 mol% Mn3O4 added 6YSZ ceramics after annealing at 1300 °C for 60 cycles in a reductive atmosphere by transmission electron microscopy. Furthermore, a single cubic ZrO2 phase existed stably as Mn3O4 added 10YSZ ceramics was annealed at 1300 °C for 60 cycles in reductive atmosphere.

Microstructure and dielectric properties of Zn2Ti3O8 films deposited on Pt/Cr/SiO2/Si via a DC reactive magnetron co-sputtering method using zinc and titanium metal targets in O2/Ar atmosphere are investigated. The as-deposited Zn–Ti–O film has an amorphous microstructure. A single Zn2Ti3O8 phase appeared when the films were annealed at 500 °C and 600 °C for 1 h. As the temperature further increased to 700 and 800 °C, it was found that Zn2Ti3O8 and ZnTiO3 phases coexisted. A phase transformation from cubic Zn2Ti3O8 and rhombohedral ZnTiO3 to cubic Zn2TiO4 and rutile TiO2 was observed while a further increase in temperature up to 900 °C. The heat treatment also induces a change in the surface morphology of the thin films observed by scanning electron microscopy. Transmission electron microscopy examination indicated that the film annealed at 700 °C was composed of Zn2Ti3O8 and ZnTiO3 with fine and large grains in microstructure, respectively. The study also reveals that the dielectric constant of the films depends on the annealing temperature. When annealing at 600 °C, the Zn2Ti3O8 films has the following properties at 1 MHz: dielectric constant = 32.9, tan δ = 0.022.

This paper presents the developing of a low-cost eye-tracking system by modifying the commercial-over-the-shelf camera to integrate with the proper-tuned open source drivers and the user-defined application programs. The system configuration is proposed and the gaze-tracking approximated by the least square polynomial mapping is described. Comparisons between other low-cost systems as well as commercial system are provided. Our system obtained the highest image capturing rate of 180 frames per second, and the ISO 9241-Part 9 test performance favored our system, in terms of Response time and Correct response rate. Currently, we are developing gaze-tracking accuracy application. The real time gaze-tracking and the Head Movement Estimation are the issues in future work.

To evaluate sex differences in mild traumatic brain injury (MTBI) with working memory functional magnetic resonance (MR) imaging.Research ethics committee approval and patient written informed consent were obtained. Working memory brain activation patterns were assessed with functional MR imaging in 30 patients (15 consecutive men and 15 consecutive women) with MTBI and 30 control subjects (15 consecutive men and 15 consecutive women). Two imaging studies were performed in patients: the initial study, which was performed within 1 month after the injury, and a follow-up study, which was performed 6 weeks after the first study. For each participant, digit span and continuous performance testing were performed before functional MR imaging. Clinical data were analyzed by using Kruskal-Wallis, Mann-Whitney U, Wilcoxon signed rank, and Fisher exact tests. Within- and between-group differences of functional MR imaging data were analyzed with one- and two-sample t tests, respectively.Among female participants, the total digit span score was lower in the MTBI group than in the control group (P = .044). In initial working memory functional MR imaging studies, hyperactivation was found in the male MTBI group and hypoactivation was found in the female MTBI group compared with control male and female groups, respectively. At the 6-week follow-up study, the female MTBI group showed persistent hypoactivation, whereas the male MTBI group showed a regression of hyperactivation at visual comparison of activation maps. The male MTBI group was also found to have a higher initial ß value than the male control group (P = .040), and there was no significant difference between the male MTBI group and the male control group (P = .221) at follow-up evaluation, which was comparable to findings on activation maps. In the female MTBI group, average ß values at both initial and follow-up studies were lower compared with those in the female control group but were not statistically significant (P = .663 and P = .191, respectively).Female patients with MTBI had lower digit span scores than did female control subjects, and functional MR imaging depicted sex differences in working memory functional activation; hypoactivation with nonrecovery of activation change at follow-up studies may suggest a worse working memory outcome in female patients with MTBI.

Background and purposeMR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique.Material and methodTwo intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis.ResultThe Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses.ConclusionsThe Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses.

Since the early 1980s, most electronics have relied on the use of complementary metal–oxide–semiconductor (CMOS) transistors. However, the principles of CMOS operation, involving a switchable semiconductor conductance controlled by an insulating gate, have remained largely unchanged, even as transistors are miniaturized to sizes of 10 nanometres. We investigated what dimensionally scalable logic technology beyond CMOS could provide improvements in efficiency and performance for von Neumann architectures and enable growth in emerging computing such as artifical intelligence. Such a computing technology needs to allow progressive miniaturization, reduce switching energy, improve device interconnection and provide a complete logic and memory family. Here we propose a scalable spintronic logic device that operates via spin–orbit transduction (the coupling of an electron’s angular momentum with its linear momentum) combined with magnetoelectric switching. The device uses advanced quantum materials, especially correlated oxides and topological states of matter, for collective switching and detection. We describe progress in magnetoelectric switching and spin–orbit detection of state, and show that in comparison with CMOS technology our device has superior switching energy (by a factor of 10 to 30), lower switching voltage (by a factor of 5) and enhanced logic density (by a factor of 5). In addition, its non-volatility enables ultralow standby power, which is critical to modern computing. The properties of our device indicate that the proposed technology could enable the development of multi-generational computing. A scalable spintronic device operating via spin–orbit transduction and magnetoelectric switching and using advanced quantum materials shows non-volatility and improved performance and energy efficiency compared with CMOS devices.