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Background Zinc finger and BTB domain-containing protein 12 (ZBTB12) is a predicted transcription factor with potential role in hematopoietic development. Recent evidence linked low methylation level of ZBTB12 exon1 to myocardial infarction (MI) risk. However, the role of ZBTB12 in the pathogenesis of MI and cardiovascular disease in general is not yet clarified. We investigated the relation between ZBTB12 methylation and several blood parameters related to cardio-cerebrovascular risk in an Italian family-based cohort. Results ZBTB12 methylation was analyzed on white blood cells from the Moli-family cohort using the Sequenom EpiTYPER MassARRAY (Agena). A total of 13 CpG Sequenom units were analyzed in the small CpG island located in the only translated ZBTB12 exon. Principal component analysis (PCA) was performed to identify groups of CpG units with similar methylation estimates. Linear mixed effect regressions showed a positive association between methylation of ZBTB12 Factor 2 (including CpG units 8, 9–10, 16, 21) and TNF-ɑ stimulated procoagulant activity, a measure of procoagulant and inflammatory potential of blood cells. In addition, we also found a negative association between methylation of ZBTB12 Factor 1 (mainly characterized by CpG units 1, 3–4, 5, 11, and 26) and white blood cell and granulocyte counts. An in silico prediction analysis identified granulopoiesis- and hematopoiesis-specific transcription factors to potentially bind DNA sequences encompassing CpG1, CpG3–4, and CpG11. Conclusions ZBTB12 hypomethylation is linked to shorter TNF-ɑ stimulated whole blood coagulation time and increased WBC and granulocyte counts, further elucidating the possible link between ZBTB12 methylation and cardiovascular disease risk. Electronic supplementary material The online version of this article (10.1186/s13148-019-0665-6) contains supplementary material, which is available to authorized users.

BackgroundPlatelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation.PEAR1variants were associated with differential platelet response to activation and cardiovascular outcomes. We aimed at investigating the link betweenPEAR1methylation and platelet and leukocyte function markers in a family-based population.ResultsWe measuredPEAR1methylation in 605 Moli-family participants with available blood counts, plasma P-selectin and C-reactive protein, whole blood platelet P-selectin, and platelet-leukocyte mixed conjugate measurements. We performed principal component analysis (PCA) to identify groups of highly correlated CpG sites. We used linear mixed regression models (using age, gender, BMI, smoking, alcohol drinking, being a proband for family recruitment, being a member of myocardial infarction (MI) family as fixed effects, and family as a random effect) to evaluate associations betweenPEAR1methylation and phenotypes.PEAR1methylation Factor2, characterized by the previously identified megakaryocyte-specific CpG sites, was inversely associated with platelet-monocyte conjugates, P-selectin, and WBC counts, while positively associated with the platelet distribution width (PDW) and with leukocyte CD11b and L-selectin. Moreover,PEAR1Factor2 methylation was negatively associated with INFLAscore, a low-grade inflammation score. The latter was partially mediated by thePEAR1methylation effect on platelet variables.PEAR1methylation association with WBC measurements and INFLAscore was confirmed in the independent cohort FLEMENGHO.ConclusionsWe report a significant link between epigenetic signatures in a platelet functional gene and inflammation-dependent platelet function variability measured in two independent cohorts.

La0.8Sr0.2Ga0.8Mg0.2O3- (LSGM) based fuel cells infiltrated with different metal catalysts were fabricated and tested both in H2 and CH4/CO2 mixture. Ni, Co, Ni-Cu, Ni-Co LSGM impregnated powders were investigated for the dry reforming of methane reaction (DRM) (CH4+CO22CO+2H2). The catalytic activity for CH4 and CO2 conversion followed the order NiNi-Co>Co>Ni-Cu. Both Ni and Ni-Co catalysts, investigated versus time (50 hours) on stream of CH4/CO2=1.5 at 800°C, did not show any sign of deactivation indicating their stability toward coke deposition. Anyway, evidence of few carbon filaments were revealed by SEM micrographs and the carbon amount evaluated by TG-DTA analysis. Ni-LSGM and Ni-Co LSGM cells showed regarding electrochemical performance both in H2 and CH4/CO2 mixture in the 650-750°C temperature range.

Fuel flexibility is one of the main advantages of Solid Oxide Fuel Cells (SOFCs) technology and is related to the high operating temperatures (773-1273K). SOFCs can be fed by methane, higher hydrocarbons and also bio-gas produced by the anaerobic fermentation of wastes and biomass. The composition range of purified bio-gas is 60-50% of CH4 and 50-40% of CO2. Thus, in principle biogas-fueled SOFCs can be operated with internal dry reforming reaction (DMR) (equation 1) by the presence of CO2 as reforming agent [1-3]. (1) DRM is commonly used for syn-gas production, thus catalysts are specially designed for this purpose. However, being generally composed by low metal loading and support with negligible ion-conduction they are unsuitable for the use in SOFCs anodes. Therefore, development of anodes with high activity toward the dry reforming of methane is still challenging. One way may be the preparation of cermets composed by low carbon sensitive Ni based- alloys [4] and highly ion-conductive electrolytes such as GDC [5]. In particular, among the oxygen-ion conducting electrolytes La0.8Sr0.2Ga0.8Mg0.2O3- (LSGM) showed a large ionic conductivity (ca. 0.02 Scm-1 at 600 oC), although the formation of insulating secondary phases and cations interdiffusion across the interface with electrodic layers have been often observed t temperatures ≥1100 °C [6]. Thus, the implementation of such Ni-based alloys requires the preparation of LSGM scaffold to be impregnated by the active components. In this work Ni, NiCo and NiCu supported on LSGM commercial powder were prepared by a conventional wet impregnation method. The catalysts were characterized by XRD, H2-TPR, CO2-TPD, BET and SEM. The catalytic activity for the DRM was studied into a quartz tubular reactor as a function of temperature and CH4/CO2 molar ratio at high GHSV (120000mLg-1h-1) simulating the condition presents in the anodic scaffold of a anode supported LSGM based SOFCs. The catalytic activity increased in the order NiCu

Background: Few studies have addressed predictors of long-term mortality after first-ever ischaemic stroke. Methods: We prospectively collected data on 361 consecutive patients admitted to 18 neurology departments in Italy for a first-ever ischaemic stroke in 1999, categorized according to the Oxfordshire Community Stroke Project (OCSP) classification. Age, gender, risk factors, previous vascular disease, in-hospital complications, stroke severity, functional status, therapy and living place at admission, discharge and after 6 months were recorded. Follow-up was available for 97% patients at 5 years. Results: Survival probability was 91% (95% CI = 88–94) at 1 month, 84% (80–88) at 6 months and 64% (58–69) at 5 years. Mortality was higher for the TACI (total anterior circulation infarct) group compared to the other categories (p < 0.0001). Hazard ratios for 5-year mortality in the final model were: 5.4 for age ≥65 years (p < 0.0001), 2.8 for TACI (p < 0.0001), 2.7 for previous vascular disease (p < 0.01) and 1.9 for cardio-embolic risk according to the TOAST risk stratification (p < 0.05). Conclusions: Our study extends the prognostic value of the OCSP classification to 5-year survival.

This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population.

Design-driven innovation aims to release the business potential of a new type of innovation, based on a radical shift of meaning. In order to do that, it is essential to achieve a deep understanding of what meaning is, how it is possible to create (new) meaning and develop transferable methods that empower designers to transfer meaning and to design radical shifts in meaning to leap innovation-wise. In a one-week Master's class, we have approached this exploration from a phenomenological perspective, where meaning is created in interaction. The class trains students to deeply scrutinize the design of meaning. Respecting the phenomenological approach, it implements the integration of different points of view and supports the use of intuition, enabled by designing from one’s own (bodily) skills. We explain by means of an example - the skill of snowboarding - how these different elements concur to enrich a design process and build the basis for a richer result in terms of meaning and therefore innovation. Starting from the design knowledge created during the class, we designed two concepts of design interaction, a knife and a dial mechanism for phones, to show how our method can lead to disruptive shifts in meaning. We illustrate the different ways that the class’ results can be translated into design, to give insight on how to achieve radical innovation, both short term and long term. We conclude by explaining the practical impact of our method for industry.