2,034 research outputs found
Enhancing catalytic performance of AuPd catalysts towards the direct synthesis of H2O2 through incorporation of base metals
The introduction of small quantities of tertiary base metals into supported AuPd nanoparticles results in improved catalytic performance towards the direct synthesis of H2O2, compared to the bi-metallic analogue. This enhanced activity can be attributed to the electronic modification of Pd and the formation of domains of mixed Pd oxidation state. In particular the introduction of Ni is observed to result in initial rates of H2O2 synthesis, where the contribution from competitive degradation reactions is negligible, in excess of three times that achieved over the supported AuPd catalyst
Improving catalytic activity towards the direct synthesis of H2O2 through Cu incorporation into AuPd catalysts
With a focus on catalysts prepared by an excess-chloride wet impregnation procedure and supported on the zeolite ZSM-5(30), the introduction of low concentrations of tertiary base metals, in particular Cu, into supported AuPd nanoparticles can be observed to enhance catalytic activity towards the direct synthesis of H2O2. Indeed the optimal catalyst formulation (1%AuPd(0.975)Cu(0.025)/ZSM-5) is able to achieve rates of H2O2 synthesis (115 molH2O2kgcat−1h−1) approximately 1.7 times that of the bi-metallic analogue (69 molH2O2kgcat−1h−1) and rival that previously reported over comparable materials which use Pt as a dopant. Notably, the introduction of Cu at higher loadings results in an inhibition of performance. Detailed analysis by CO-DRFITS and XPS reveals that the improved performance observed over the optimal catalyst can be attributed to the electronic modification of the Pd species and the formation of domains of a mixed Pd2+/Pd0 oxidation state as well as structural changed within the nanoalloy
Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.
Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome
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Word Detection in Individual Subjects Is Difficult to Probe With Fast Periodic Visual Stimulation
Measuring cognition in single subjects presents unique challenges. On the other hand, individually sensitive measurements offer extraordinary opportunities, from informing theoretical models to enabling truly individualised clinical assessment. Here, we test the robustness of fast, periodic, and visual stimulation (FPVS), an emerging method proposed to elicit detectable responses to written words in the electroencephalogram (EEG) of individual subjects. The method is non-invasive, passive, and requires only a few minutes of testing, making it a potentially powerful tool to test comprehension in those who do not speak or who struggle with long testing procedures. In an initial study, Lochy et al. (2015) used FPVS to detect word processing in eight out of 10 fluent French readers. Here, we attempted to replicate their study in a new sample of 10 fluent English readers. Participants viewed rapid streams of pseudo-words with words embedded at regular intervals, while we recorded their EEG. Based on Lochy et al. (2015) we expected that words would elicit a steady-state response at the word-presentation frequency (2 Hz) over parieto-occipital electrode sites. However, across 40 datasets (10 participants, two conditions, and two regions of interest–ROIs), only four datasets met the criteria for a unique response to words. This corresponds to a 10% detection rate. We conclude that FPVS should be developed further before it can serve as an individually-sensitive measure of written word processing
The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
Predicció de risc de càncer de mama; Dones europees; Variant patògena heterozigotaPredicción del riesgo de cáncer de mama; Mujeres europeas; Variante patógena heterocigotaBreast cancer risk prediction; European women; Heterozygous pathogenic variantPurpose
To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.
Methods
We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.
Results
For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.
Conclusion
The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making
Tuning of catalytic sites in Pt/TiO2 catalysts for chemoselective hydrogenation of 3-nitrostyrene
The catalytic activities of supported metal nanoparticles can be tuned by appropriate design of synthesis strategies. Each step in a catalyst synthesis method can play an important role in preparing the most efficient catalyst. Here we report the careful manipulation of the post-synthetic heat treatment procedure—together with control over the metal loading—to prepare a highly efficient 0.2 wt% Pt/TiO2 catalyst for the chemoselective hydrogenation of 3-nitrostyrene. For Pt/TiO2 catalysts with 0.2 and 0.5 wt% loading levels, reduction at 450 °C induces the coverage of TiOx over Pt nanoparticles through a strong metal–support interaction, which is detrimental to their catalytic activities. However, this can be avoided by following calcination treatment with reduction (both at 450 °C), allowing us to prepare an exceptionally active catalyst. Detailed characterization has revealed that the peripheral sites at the Pt/TiO2 interface are the most likely active sites for this hydrogenation reactio
Tuning of catalytic sites in Pt/TiO<sub>2</sub> catalysts for the chemoselective hydrogenation of 3-nitrostyrene
The catalytic activities of supported metal nanoparticles can be tuned by appropriate design of synthesis strategies. Each step in a catalyst synthesis method can play an important role in preparing the most efficient catalyst. Here we report the careful manipulation of the post-synthetic heat treatment procedure—together with control over the metal loading—to prepare a highly efficient 0.2 wt% Pt/TiO2 catalyst for the chemoselective hydrogenation of 3-nitrostyrene. For Pt/TiO2 catalysts with 0.2 and 0.5 wt% loading levels, reduction at 450 °C induces the coverage of TiOx over Pt nanoparticles through a strong metal–support interaction, which is detrimental to their catalytic activities. However, this can be avoided by following calcination treatment with reduction (both at 450 °C), allowing us to prepare an exceptionally active catalyst. Detailed characterization has revealed that the peripheral sites at the Pt/TiO2 interface are the most likely active sites for this hydrogenation reactio
Tuning of catalytic sites in Pt/TiO<sub>2</sub> catalysts for the chemoselective hydrogenation of 3-nitrostyrene
The catalytic activities of supported metal nanoparticles can be tuned by appropriate design of synthesis strategies. Each step in a catalyst synthesis method can play an important role in preparing the most efficient catalyst. Here we report the careful manipulation of the post-synthetic heat treatment procedure—together with control over the metal loading—to prepare a highly efficient 0.2 wt% Pt/TiO2 catalyst for the chemoselective hydrogenation of 3-nitrostyrene. For Pt/TiO2 catalysts with 0.2 and 0.5 wt% loading levels, reduction at 450 °C induces the coverage of TiOx over Pt nanoparticles through a strong metal–support interaction, which is detrimental to their catalytic activities. However, this can be avoided by following calcination treatment with reduction (both at 450 °C), allowing us to prepare an exceptionally active catalyst. Detailed characterization has revealed that the peripheral sites at the Pt/TiO2 interface are the most likely active sites for this hydrogenation reaction.</p
Deterministic evolution and stringent selection during preneoplasia
The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours
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