Developing efficient and low‐cost electrocatalysts for the oxygen evolution reaction (OER) is of paramount importance to many chemical and energy transformation technologies. The diversity and ...flexibility of metal oxides offer numerous degrees of freedom for enhancing catalytic activity by tailoring their physicochemical properties, but the active site of current metal oxides for OER is still limited to either metal ions or lattice oxygen. Here, a new complex oxide with unique hexagonal structure consisting of one honeycomb‐like network, Ba4Sr4(Co0.8Fe0.2)4O15 (hex‐BSCF), is reported, demonstrating ultrahigh OER activity because both the tetrahedral Co ions and the octahedral oxygen ions on the surface are active, as confirmed by combined X‐ray absorption spectroscopy analysis and theoretical calculations. The bulk hex‐BSCF material synthesized by the facile and scalable sol–gel method achieves 10 mA cm−2 at a low overpotential of only 340 mV (and small Tafel slope of 47 mV dec−1) in 0.1 m KOH, surpassing most metal oxides ever reported for OER, while maintaining excellent durability. This study opens up a new avenue to dramatically enhancing catalytic activity of metal oxides for other applications through rational design of structures with multiple active sites.
A new complex oxide with unique hexagonal structure consisting of one ordered (Co/Fe)O15 cluster, Ba4Sr4(Co0.8Fe0.2)4O15 (hex‐BSCF), is reported to show ultrahigh oxygen evolution reaction (OER) electrocatalytic activity because both the tetrahedral Co ions and the octahedral oxygen ions on the surface are active, as confirmed by combined X‐ray absorption spectroscopy analysis and theoretical calculations.
Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence ...indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2
, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.
Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%–4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug ...target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC.
Eligible patients ≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2 with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b.i.d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats.
Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). The median treatment duration was 10.4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10.4–33.0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% confidence interval, 3.8–11.9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%).
MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).
•This study provides first evidence of clinically meaningful antitumor activity of capmatinib in MET-dysregulated NSCLC.•Accurate biomarker selection of the patients is needed to identify the patients expected to respond better to capmatinib.•MET amplification GCN ≥6 and/or METex14 skipping are strong predictive biomarkers for response to capmatinib.•Overexpression alone cannot be considered as a reliable biomarker to predict the efficacy of capmatinib.•Capmatinib is well tolerated with the majority of the AEs grade 1 and 2.
Understanding how materials that catalyse the oxygen evolution reaction (OER) function is essential for the development of efficient energy-storage technologies. The traditional understanding of the ...OER mechanism on metal oxides involves four concerted proton-electron transfer steps on metal-ion centres at their surface and product oxygen molecules derived from water. Here, using in situ
O isotope labelling mass spectrometry, we provide direct experimental evidence that the O
generated during the OER on some highly active oxides can come from lattice oxygen. The oxides capable of lattice-oxygen oxidation also exhibit pH-dependent OER activity on the reversible hydrogen electrode scale, indicating non-concerted proton-electron transfers in the OER mechanism. Based on our experimental data and density functional theory calculations, we discuss mechanisms that are fundamentally different from the conventional scheme and show that increasing the covalency of metal-oxygen bonds is critical to trigger lattice-oxygen oxidation and enable non-concerted proton-electron transfers during OER.
We use a layered solution crystal growth technique to synthesize high-quality single crystals of phenylalkylammonium lead iodide organic/inorganic hybrid compounds. Single-crystal X-ray diffraction ...reveals low-dimensional structures consisting of inorganic sheets separated by bilayers of the organic cations. The shortest alkyls yield two-dimensional structures consisting of inorganic sheets of corner-sharing PbI6-octahedra. However, the longer alkyls induce both corner- and face-sharing of the PbI6-octahedra, and form new compounds. Density functional theory calculations including spin–orbit coupling show quantum confinement in two dimensions for the shorter alkyls, and in one dimension for the longer alkyls, respectively. The face-sharing PbI6-octahedra create a confinement leading to effectively one-dimensional behavior. These confinement effects are responsible for the observed peak shifts in photoluminescence for the different phenylalkylammonium lead iodide hybrids. Our results show how the connectivity of the octahedra leads to confinement effects that directly tune the optical band gap.
Purpose
The purpose of this paper is to explore the relationship between transformational leadership and employees’ work engagement based on fit theory. The paper reports an investigation into the ...way in which employees’ perceptions of transformational leadership and person-job fit affect their work engagement.
Design/methodology/approach
To test the authors’ hypotheses, the authors performed structure equation modeling with maximum likelihood estimation on Mplus with bootstrapping proposed by Hayes (2009) with data from 691 full-time employees in China.
Findings
The results indicate that transformational leadership has as significant influence on employees’ work engagement as person-job fit in China. Moreover, employees’ perception of person-job fit is found to partially mediate the relationship between transformational leadership and employees’ work engagement.
Research limitations/implications
There is a possible bias arising from the use of cross-sectional data. However, certain methods were implemented to minimize it, including survey design and data analysis.
Practical implications
The paper proposes a number of practical implications for policy makers, HR managers and transformational leaders relating to issues associated with improving levels of employee engagement.
Originality/value
The study contributes to developing leadership and engagement theory by examining a previously unexplored mediator – person-job fit – in a neglected cultural setting. This study promises to open new research avenues in this area.
Gastric cancer is one of the leading causes of cancer death worldwide. Previous studies demonstrated that activation of STAT3 is crucial for the development and progression of gastric cancer. ...However, the role of STAT3 in neuronal related gene methylation in gastric cancer has never been explored. In this study, by using DNA methylation microarray, we identified a potential STAT3 target, C11orf87, showing promoter hypomethylation in gastric cancer patients with lower STAT3 activation and AGS gastric cancer cell lines depleted with STAT3 activation. Although C11orf87 methylation is independent of its expression, ectopic expression of a constitutive activated STAT3 mutant upregulated its expression in gastric cancer cell line. Further bisulfite pyrosequencing demonstrated a progressive increase in DNA methylation of this target in patient tissues from gastritis, intestinal metaplasia, to gastric cancer. Intriguingly, patients with higher C11orf87 methylation was associated with better survival. Furthermore, hypermethylation of C11orf87 was also frequently observed in other GI cancers, as compared to their adjacent normal tissues. These results suggested that C11orf87 methylation may serve as a biomarker for diagnosis and prognosis of GI cancers, including gastric cancer. We further postulated that constitutive activation of STAT3 might be able to epigenetically silence C11orf87 as a possible negative feedback mechanism to protect the cells from the overactivation of STAT3. Targeted inhibition of STAT3 may not be appropriate in gastric cancer patients with promoter hypermethylation of C11orf87.
We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC).
The ...PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected toin vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling.
The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations ofFGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib.
FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.
We present an interpretable implementation of the autoencoding algorithm, used as an anomaly detector, built with a forest of deep decision trees on FPGA, field programmable gate arrays. Scenarios at ...the Large Hadron Collider at CERN are considered, for which the autoencoder is trained using known physical processes of the Standard Model. The design is then deployed in real-time trigger systems for anomaly detection of unknown physical processes, such as the detection of rare exotic decays of the Higgs boson. The inference is made with a latency value of 30 ns at percent-level resource usage using the Xilinx Virtex UltraScale+ VU9P FPGA. Our method offers anomaly detection at low latency values for edge AI users with resource constraints.
Top Management Team Diversity Homberg, Fabian; Bui, Hong T. M.
Group & organization management,
08/2013, Letnik:
38, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Empirical research investigating the impact of top management team (TMT) diversity on executives’ decision making has produced inconclusive results. To synthesize and aggregate the results on the ...diversity-performance link, a meta-regression analysis (MRA) is conducted. It integrates more than 200 estimates from 53 empirical studies investigating TMT diversity and its impact on the quality of executives’ decision making as reflected in corporate performance. The analysis contributes to the literature by theoretically discussing and empirically examining the effects of TMT diversity on corporate performance. Our results do not show a link between TMT diversity and performance but provide evidence for publication bias. Thus, the findings raise doubts on the impact of TMT diversity on performance.
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