Chemical modeling of acid-base properties of soluble biopolymers derived from municipal waste treatment materials

This work reports a study of the proton-binding capacity of biopolymers obtained from different materials supplied by a municipal biowaste treatment plant located in Northern Italy. One material was the anaerobic fermentation digestate of the urban wastes organic humid fraction. The others were the compost of home and public gardening residues and the compost of the mix of the above residues, digestate and sewage sludge. These materials were hydrolyzed under alkaline conditions to yield the biopolymers by saponification. The biopolymers were characterized by 13C NMR spectroscopy, elemental analysis and potentiometric titration. The titration data were elaborated to attain chemical models for interpretation of the proton-binding capacity of the biopolymers obtaining the acidic sites concentrations and their protonation constants. The results obtained with the models and by NMR spectroscopy were elaborated together in order to better characterize the nature of the macromolecules. The chemical nature of the biopolymers was found dependent upon the nature of the sourcing materials

Local Study of Lithiation and Degradation Paths in LiMn2O4 Battery Cathodes: Confocal Raman Microscopy Approach

Lithium manganese-based cathodes are widely used in rechargeable batteries due to their low cost, safety, and ecological stability. On the other hand, fast capacity fade occurs in LiMn2O4 mainly because of the induced manganese dissolution and formation of additional phases. Confocal Raman microscopy provides many opportunities for sensitive and spatially resolved structural studies of micro- and nanoscale phenomena. Here, we demonstrate advantages of confocal Raman spectroscopy approach for uncovering the mechanisms of lithiation/delithiation and degradation in LiMn2O4 commercial cathodes. The analysis of Raman spectra for inspecting local lithiation state and phase composition is proposed and exploited for the visualization of the inhomogeneous distribution of lithium ions. The cycling of cathodes is shown to be followed by the formation and dissolution of the Mn3O4 phase and local disturbance of the lithiation state. These processes are believed to be responsible for the capacity fade in the commercial batteries

Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ

The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction. YAP-induced mammary stem/progenitor cells show molecular and functional properties similar to endogenous MaSCs, including organoid formation and mammary gland reconstitution after transplantation. Because YAP/TAZ function is also important for self-renewal of endogenous stem cells in culture, our findings have implications for understanding the molecular determinants of the somatic stem cell state

Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties

Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer biology. We found that receptor tyrosine kinase (RTK)–Ras oncogenes reprogram normal, freshly explanted primary mouse and human cells into tumour precursors, in a process requiring increased force transmission between oncogene-expressing cells and their surrounding extracellular matrix. Microenvironments approximating the normal softness of healthy tissues, or blunting cellular mechanotransduction, prevent oncogene-mediated cell reprogramming and tumour emergence. However, RTK–Ras oncogenes empower a disproportional cellular response to the mechanical properties of the cell’s environment, such that when cells experience even subtle supra-physiological extracellular-matrix rigidity they are converted into tumour-initiating cells. These regulations rely on YAP/TAZ mechanotransduction, and YAP/TAZ target genes account for a large fraction of the transcriptional responses downstream of oncogenic signalling. This work lays the groundwork for exploiting oncogenic mechanosignalling as a vulnerability at the onset of tumorigenesis, including tumour prevention strategies

Electrochemical strain microscopy time spectroscopy: Model and experiment on LiMn2O4

Electrochemical Strain Microscopy (ESM) can provide useful information on ionic diffusion in solids at the local scale. In this work, a finite element model of ESM measurements was developed and applied to commercial lithium manganese (III,IV) oxide (LiMn2O4) particles. ESM time spectroscopy was used, where a direct current (DC) voltage pulse locally disturbs the spatial distribution of mobile ions. After the pulse is off, the ions return to equilibrium at a rate which depends on the Li diffusivity in the material. At each stage, Li diffusivity is monitored by measuring the ESM response to a small alternative current (AC) voltage simultaneously applied to the tip. The model separates two different mechanisms, one linked to the response to DC bias and another one related to the AC excitation. It is argued that the second one is not diffusion-driven hut is rather a contribution of the sum of several mechanisms with at least one depending on the lithium ion concentration explaining the relaxation process. With proper fitting of this decay, diffusion coefficients of lithium hosts could be extracted. Additionally, the effect of phase transition in LiMn2O4 is taken into account, explaining some experimental observations. (C) 2015 AIP Publishing LLC

Disease family history and modification of breast cancer risk in common BRCA2 variants

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Bleeding in Patients Treated With Ticagrelor or Clopidogrel Before Coronary Artery Bypass Grafting

BackgroundWe evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y12 inhibitors.MethodsAll patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates.ResultsOf 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score–matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p = 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p = 0.031).ConclusionsIn patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.</div

Comparative Analysis of Prothrombin Complex Concentrate and Fresh Frozen Plasma in Coronary Surgery

BackgroundRecent studies suggested that prothrombin complex concentrate (PCC) might be more effective than fresh frozen plasma (FFP) to reduce red blood cell (RBC) transfusion requirement after cardiac surgery.MethodsThis is a comparative analysis of 416 patients who received FFP postoperatively and 119 patients who received PCC with or without FFP after isolated coronary artery bypass grafting (CABG).ResultsMixed-effects regression analyses adjusted for multiple covariates and participating centres showed that PCC significantly decreased RBC transfusion (67.2% vs. 87.5%, adjusted OR 0.319, 95%CI 0.136–0.752) and platelet transfusion requirements (11.8% vs. 45.2%, adjusted OR 0.238, 95%CI 0.097–0.566) compared with FFP. The PCC cohort received a mean of 2.7 ± 3.7 (median, 2.0, IQR 4) units of RBC and the FFP cohort received a mean of 4.9 ± 6.3 (median, 3.0, IQR 4) units of RBC (adjusted coefficient, −1.926, 95%CI −3.357–0.494). The use of PCC increased the risk of KDIGO (Kidney Disease: Improving Global Outcomes) acute kidney injury (41.4% vs. 28.2%, adjusted OR 2.300, 1.203–4.400), but not of KDIGO acute kidney injury stage 3 (6.0% vs. 8.0%, OR 0.850, 95%CI 0.258–2.796) when compared with the FFP cohort.ConclusionsThese results suggest that the use of PCC compared with FFP may reduce the need of blood transfusion after CABG.</p