Study of the nanometric grain size distribution in iron compacts obtained by mechanical milling

Postprint (published version

Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges

© Schattauer 2015. The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class-effect. In lay terms “cancers follow bleeding”, which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail

Study of the nanometric grain size distribution in iron compacts obtained by mechanical milling

A study has been carried out on the grain size distribution of cylindrical compacts obtained by consolidation of iron powder severely deformed by mechanical milling. Consolidation has been performed in two consecutive steps: cold and hot conditions. The hot one was done at two temperatures, namely 425 and 475ºC. After milling, the iron powder has a grain size of 8 nm (± 4 nm) with an average hardness of 800 HV. After hot compaction the grain size increases up to 50 nm, especially at 475ºC where a small fraction of grains reach larger values than the average. The grain size was evaluated by two different techniques, X-Ray Diffraction and Transmission Electron Microscopy. Results showed some differences between both methods. The advantage of using TEM is that grain size distribution, and not only the average size, can be obtained. Small discs were also obtained from the compacted specimen in order to fracture them on a “ball on three balls” equipment. The fracture behaviour of the samples was then studied by SEM.Postprint (published version

Full left ventricular coverage is essential for the accurate quantification of the area- at- risk by T1 and T2 mapping

T2-weighted cardiovascular magnetic resonance (CMR) using a 3-slice approach has been shown to accurately quantify the edema-based area-at-risk (AAR) in ST-segment elevation myocardial infarction (STEMI). We aimed to compare the performance of a 3-slice approach to full left ventricular (LV) coverage for the AAR by T1 and T2 mapping and MI size. Forty-eight STEMI patients were prospectively recruited and underwent a CMR at 4 ± 2 days. There was no difference between the AARfull LV and AAR3-slices by T1 (P = 0.054) and T2-mapping (P = 0.092), with good correlations but small biases and wide limits of agreements (T1-mapping: N = 30, R2 = 0.85, bias = 1.7 ± 9.4% LV; T2-mapping: N = 48, R2 = 0.75, bias = 1.7 ± 12.9% LV). There was also no significant difference between MI size3-slices and MI sizefull LV (P = 0.93) with an excellent correlation between the two (R2 0.92) but a small bias of 0.5% and a wide limit of agreement of ±7.7%. Although MSI was similar between the 2 approaches, MSI3-slices performed poorly when MSI was <0.50. Furthermore, using AAR3-slices and MI sizefull LV resulted in ‘negative’ MSI in 7/48 patients. Full LV coverage T1 and T2 mapping are more accurate than a 3-slice approach for delineating the AAR, especially in those with MSI < 0.50 and we would advocate full LV coverage in future studies

Internalization of Bacillus intermedius ribonuclease (BINASE) induces human alveolar adenocarcinoma cell death

Ribonuclease (RNase) treatment represents a novel mechanism based approach to anticancer therapy as an alternative to the DNA damaging drugs commonly used in clinical practice. Apart from their ribonucleolytic activity, cytotoxic effects have attracted a considerable attention to RNases because of their potential as selective agents for treatment of certain malignancies. Among these enzymes, Binase, an RNase from Bacillus intermedius, has shown promising results. Here, we have found that binase selectively attacked human A549 alveolar adenocarcinoma cells to trigger an apoptotic response, whereas normal lung epithelial cells LEK were not affected by the ribonuclease. The tumor transformation led to the modification of certain cellular characteristics causing cell sensitivity to binase. Although a general mode for RNases cytotoxicity includes their penetration into the cell, translocation to the cytosol and degradation of ribonucleic acid, many aspects of this process have not been fully elucidated. Our data revealed the following time-dependent changes induced by binase in A549 cells: (a) fast permanent internalization of the enzyme during the first hours of treatment; (b) temporary increase in cellular permeability for macromolecules during the 4-6hof treatment; (c) apoptotic alterations in population after 24hand (d) DNA fragmentation and cell death after 72hof treatment with binase. Elucidation of these molecular strategies used by this promising toxin provides us essential information for the development of new anticancer drugs. © 2013 Elsevier Ltd

RNase1 as a potential mediator of remote ischaemic preconditioning for cardioprotection

© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. OBJECTIVES: Remote ischaemic preconditioning (RIPC) is a non-invasive and virtually cost-free strategy for protecting the heart against acute ischaemia-reperfusion injury (IRI). We have recently shown that the inhibition of extracellular RNA (eRNA) using non-toxic RNase1 protected the heart against acute IRI, reduced myocardial infarct (MI) size and preserved left ventricular systolic function in rodent animal MI models. Based on this previous work in animals, the role of the eRNA/RNase1 system in cardiac RIPC in humans should be defined. METHODS: Fourteen patients underwent cardiac surgery without RIPC; from each patient, six separate 5 ml blood specimens from radial artery and two blood specimens from coronary sinus at different time points during heart surgery were taken. Six healthy donors received RIPC (4 × 5 min upper limb ischaemia); blood parameters were quantified before and after RIPC. Twelve patients underwent cardiac surgery of which 6 received RIPC, whereas the remaining 6 were exposed to sham procedure. Circulating eRNA was quantified in plasma from arterial and coronary sinus blood obtained from patients undergoing cardiac by standard procedures. Tumour necrosis factor-α (TNF-α) production by heart tissue was assessed by enzyme-linked immuno-sorbent assay; RNase activity was quantified by an enzymatic assay. RESULTS: Before surgery, eRNA levels were similar in both groups (14 ± 6 vs 13 ± 5 ng/ml; P = 0.9967). In patients without RIPC, arterial eRNA levels rose during surgery (87 ± 12 ng/ml) and peaked after (127 ± 11 ng/ml) aortic declamping; accordingly, eRNA levels in coronary sinus blood were significantly higher (206 ± 32 ng/ml; P = 0.0129) than that in radial artery. Moreover, significant elevation of TNF-α (36 ± 6 ng/ml; P = 0.0059) particularly in coronary sinus blood after opening of the aortic clamping was observed. Interestingly, applying a RIPC protocol significantly increased levels of plasma endogenous vascular RNase1 by >7-fold, and the levels of arterial (31 ± 7 ng/ml; P = 0.0024) and coronary sinus (37 ± 9 ng/ml; P < 0.0001) circulating eRNA, as well as circulating TNF-α (20 ± 4 ng/ml; P = 0.0050) levels were significantly reduced. CONCLUSIONS: Upon RIPC, the level of cardioprotective RNase1 increased, while the concentration of damaging eRNA and TNF-α decreased. The present findings imply a significant contribution of the RIPC-dependent (endothelial) RNase1 for improving the outcome of cardiac surgery. However, the exact mechanism of RNase1-induced cardioprotection still remains to be explored

Desert dust remote sensing with the new zenith looking narrow‐band radiometer based system (ZEN)

Comunicación presentada en: TECO-2016 (Technical Conference on Meteorological and Environmental Instruments and Methods of Observation) celebrada en Madrid, del 27 al 30 de septiembre de 2016.This work has been developed within the framework of the activities of the World Meteorological Organization (WMO) Commission for Instruments and Methods of Observations (CIMO) Izaña Testbed for Aerosols and Water Vapor Remote Sensing Instruments. AERONET sun photometers at Izaña have been calibrated within the AERONET Europe TNA, supported by the European Community ‐ Research Infrastructure Action under the FP7 ACTRIS grant agreement no. 262254

Tight-binding parameters for charge transfer along DNA

We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The $\pi$ molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the $\pi$ molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table