Highly Tunable Intrinsic Exchange Bias from Interfacial Reconstruction in Epitaxial NixCoyFe3-x-yO4(111)/{\alpha}-Al2O3(0001) Thin Films

Intrinsic exchange bias up to 12.6 kOe is observed in NixCoyFe3-x-yO4(111)/{\alpha}-Al2O3(0001) (0<=x+y<=3) epitaxial thin films where 0.15<=y<=2. An interfacial layer of rock-salt structure emerges between NixCoyFe3-x-yO4 thin films and {\alpha}-Al2O3 substrates and is proposed as the antiferromagnetic layer unidirectionally coupled with ferrimagnetic NixCoyFe3-x-yO4. In NiCo2O4(111)/{\alpha}-Al2O3(0001) films, results of reflection high energy electron diffraction, X-ray photoelectron spectroscopy, X-ray reflectometry, and polarized neutron reflectometry support that the interfacial layer is antiferromagnetic NixCo1-xO (0.32<=x<=0.49) of rock-salt structure; the interfacial layer and exchange bias can be controlled by growth oxygen pressure revealing the key role of oxygen in the mechanism of the interfacial reconstruction. This work establishes a family of intrinsic exchange bias materials with great tunability by stoichiometry and growth parameters and emphasizes the strategy of interface engineering in controlling material functionalities.Comment: Main Text: 14 pages, 5 figures; Supplemental Materials: 12 pages, 11 figure

Duality of switching mechanisms and transient negative capacitance in improper ferroelectrics

The recent discovery of transient negative capacitance has sparked an intense debate on the role of homogeneous and inhomogeneous mechanisms in polarizations switching. In this work, we report observation of transient negative capacitance in improper ferroelectric h-YbFeO3 films in a resistor-capacitor circuit, and a concaved shape of anomaly in the voltage wave form, in the early and late stage of the polarizations switching respectively. Using a phenomenological model, we show that the early-stage negative capacitance is likely due to the inhomogeneous switching involving nucleation and domain wall motion, while the anomaly at the late stage, which appears to be a reminiscent negative capacitance is the manifestation of the thermodynamically unstable part of the free-energy landscape in the homogeneous switching. The complex free-energy landscape in hexagonal ferrites may be the key to cause the abrupt change in polarization switching speed and the corresponding anomaly. These results reconcile the two seemingly conflicting mechanisms in the polarization switching and highlight their different roles at different stages. The unique energy-landscape in hexagonal ferrites that reveals the dual switching mechanism suggests the promising application potential in terms of negative capacitance.Comment: 14 pages,5 figure

STGAT-MAD: Spatial-Temporal Graph Attention Network for Multivariate Time Series Anomaly Detection

Anomaly detection in multivariate time series data is challenging due to complex temporal and feature correlations and heterogeneity. This paper proposes a novel unsupervised multi-scale stacked spatial-temporal graph attention network for multivariate time series anomaly detection (STGATMAD). The core of our framework is to coherently capture the feature and temporal correlations among multivariate time-series data with stackable STGAT networks. Meanwhile, a multi-scale input network is exploited to capture the temporal correlations in different time-scales. Experiments on a new wind turbine dataset (built and released by us) and three public datasets show that our method detects anomalies more accurately than baseline approaches and provide interpretability through observing the attention score among multiple sensors and different times

GW501516, a PPARδ Agonist, Ameliorates Tubulointerstitial Inflammation in Proteinuric Kidney Disease via Inhibition of TAK1-NFκB Pathway in Mice

Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(−). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Growth and Emergent Functionalities of Oxide Thin Films Utilizing Interface Engineering

Complex oxide interfaces have offered intriguing novel emergent phenomena and multiple functionalities through interfacial reconstructions of spin, orbital, charge, and lattice degrees of freedom. Interface engineering via manipulating interfacial interaction, defects and multiple interfacial quantum charges and orders constitutes the essential method and technique to achieve desired functionalities in oxide heterostructures. In this thesis, shown are two examples of utilizing interfacial reconstruction and interfacial strain engineering to achieve intrinsic exchange bias and realize epitaxial growth of mixed-valence hexagonal manganite thin films, respectively. Firstly, we demonstrated intrinsic exchange bias induced by interfacial reconstruction in NixCoyFe3-x-yO4(111)/-Al2O3(0001) (0£x+y£3) tunable beyond the coercivity. The “hidden” antiferromagnet is proposed to be the rock-salt CoO in the interfacial layer, supported by the data of reflection high energy electron diffraction (RHEED), magnetization characterization, X-ray photoemission spectroscopy, X-ray reflectometry and polarized neutron reflectometry. Such interfacial reconstruction and intrinsic exchange bias can be tuned by Co concentration y and the growth oxygen pressure. This study establishes new material platforms to study novel interfacial structural and magnetic states supporting potential applications in magnetic storage and spintronics and highlight the powerful interface engineering strategy in manipulating material functionalities. Secondly, we have managed to stabilize h-Lu1-xCaxMnO3 (x=0.1,0.2,0.3,0.4,0.5) epitaxial thin films over sapphire and YSZ substrates via pre-depositing a 1 nm h-ReFeO3 or h-ReMnO3 (Re= Y, Ho-Lu, Sc) buffer layer. By selecting varying combinations of buffer layers and substrates, epitaxial h-Lu1-xCaxMnO3 films with both compressive and tensile strain were achieved to certain maximum thicknesses. In h-Lu1-xCaxMnO3/h-ScFeO3/α-Al2O3 samples, thickness-resolved and temperature-resolved RHEED patterns reveal that the geometric polar distortion could be boosted by the doping of Ca, when the doping concentration x 0.2, the common interface clamping effect that suppresses ferroelectric distortion in the first unit cell of h-ReMnO3 can be eliminated. This work establishes a potential quasi-2D ferroelectric system and suggests a general strain engineering method to strengthen improper ferroelectricity in the ultra-thin regime. Advisor: Xiaoshan X