Charge ordering transition in GdBaCo2O5: evidence of reentrant behavior

We present a detailed study on the charge ordering (CO) transition in GdBaCo2O5 system by combining high resolution synchrotron powder/single crystal diffraction with electron paramagnetic resonance (EPR) experiments as a function of temperature. We found a second order structural phase transition at TCO=247 K (Pmmm to Pmma) associated with the onset of long range CO. At Tmin = 1.2TCO, the EPR linewidth rapidly broadens providing evidence of spin fluctuations due to magnetic interactions between Gd3+ ions and antiferromagnetic couplings of Co2+/Co3+ sublattices. This likely indicates that, analogously to manganites, the long-range antiferromagnetic order in GdBaCo2O5 sets in at TCO. Pair distribution function (PDF) analysis of diffraction data revealed signatures of structural inhomogeneities at low temperature. By comparing the average and local bond valences, we found that above TCO the local structure is consistent with a fully random occupation of Co2+ and Co3+ in a 1:1 ratio and with a complete charge ordering below TCO. Below T = 100 K the charge localization is partially melted at the local scale, suggesting a reentrant behavior of CO. This result is supported by the weakening of superstructure reflections and the temperature evolution of EPR linewidth that is consistent with paramagnetic (PM) reentrant behavior reported in the GdBaCo2O5.5 parent compound.Comment: 30 pages, 10 figure

Crystal structure and structural phase transitions in the GdBaCo2O5.0 cobaltite

We present an accurate investigation of the prototypical rare-earth cobaltite GdBaCo2O5.0 by complementary synchrotron powder and conventional source single-crystal x-ray diffraction experiments. The correct space group (Pmmm) and the accurate crystallographic structure of this compound at room temperature (RT) have been determined. By increasing T a second-order structural-phase transition to a tetragonal structure with space group P4/mmm at T 48 331 K is found. Close to the N\ub4eel temperature (TN 48 350 K), anomalies appear in the trend of the lattice constants, suggesting that the structural phase transition is incipient at TN. A possible mechanism for this complex behavior is suggested

Functional evidence of mTORβ splice variant involvement in the pathogenesis of congenital heart defects

mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with a complex congenital heart disease and an interstitial duplication in the short arm of chromosome 1, encompassing part of the mTOR gene. Our results suggest that an intragenic mTOR microduplication might play a role in the pathogenesis of non-syndromic congenital heart defects (CHDs) due to an upregulation of mTOR/Rictor and consequently an increased phosphorylation of PI3K/AKT and MEK/ERK signaling pathways in patient-derived amniocytes. This is the first report which shows a causative role of intragenic mTOR microduplication in the etiology of an isolated complex CHD

Molecular and Functional Characterization of Three Different Postzygotic Mutations in PIK3CA-Related Overgrowth Spectrum (PROS) Patients: Effects on PI3K/AKT/mTOR Signaling and Sensitivity to PIK3 Inhibitors

BACKGROUND PIK3CA-related overgrowth spectrum (PROS) include a group of disorders that affect only the terminal portion of a limb, such as type I macrodactyly, and conditions like fibroadipose overgrowth (FAO), megalencephaly-capillary malformation (MCAP) syndrome, congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES) syndrome and Hemihyperplasia Multiple Lipomatosis (HHML). Heterozygous postzygotic PIK3CA mutations are frequently identified in these syndromes, while timing and tissue specificity of the mutational event are likely responsible for the extreme phenotypic variability observed. METHODS: We carried out a combination of Sanger sequencing and targeted deep sequencing of genes involved in the PI3K/AKT/mTOR pathway in three patients (1 MCAP and 2 FAO) to identify causative mutations, and performed immunoblot analyses to assay the phosphorylation status of AKT and P70S6K in affected dermal fibroblasts. In addition, we evaluated their ability to grow in the absence of serum and their response to the PI3K inhibitors wortmannin and LY294002 in vitro. RESULTS AND CONCLUSION: Our data indicate that patients' cells showed constitutive activation of the PI3K/Akt pathway. Of note, PI3K pharmacological blockade resulted in a significant reduction of the proliferation rate in culture, suggesting that inhibition of PI3K might prove beneficial in future therapies for PROS patients

Safety and efficacy of low-dose sirolimus in the PIK3CA-Related Overgrowth Spectrum

Purpose PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. Conclusion This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS

Thermovalorization: new technologies, impacts and mitigation strategies [Termovalorizzatori: analisi e confronto tra nuove tecnologie, impatti e strategie di mitigazione]

In recent decades the quantity (in weight and volume) of solid waste is grown so rapidly to become a real problem especially in densely urbanized areas. The disposal of Municipal Solid Waste by incineration with energy recovery (WtE) is recognized as the most suitable system to process non-recyclable waste. However in several countries there are still concerns from experts and local communities about the environmental impact of incinerators. Epidemiological studies, developed since the 80s, are still the subject of controversial discussion because the results of research often refer to old incinerators--built a few decades ago--and therefore more impactful. In fact inadequate levels of gas cleaning and combustion process control in these facilities tended to risk the health of plant workers and local environment. This situation furthermore contributes to increase public risk perception and the spread of the NIMBY (not in my backyard) syndrome while siting this unwanted but necessary facilities. Actually, new strategies as advances in emission control designs and very stringent new governmental regulations, have resulted in large reductions in the amount of emissions. So the first aim of this work has been to understand if these high perception of risk have a reason to exist also in modern and new municipal waste incinerators. The second aim is to discover if the law, the new technologies and the mitigation strategies can really set a limit on the negative impacts on human health and on environment and if is it possible to improve or increase these strategies. Work has been divided into two parts. The first part focuses on analysis of waste environmental impact regulations, of plant operation systems and of epidemiological studies results. The second part involves the examination of the actual use of regulatory instruments, the most advanced technologies and the strategies for mitigation in the most effective new concept incinerators plants. For this verification has been analyzed in detail some different incineration plants recently created or rehabilitated in the last decade. The case-studies showed that the preliminary evaluation tools and the constant control of the waste incinerator are very effective. Moreover the comparison between the maximum emission limits, the BAT and the analysis of the actual emission of the cases study has shown the effectiveness of the depuration systems currently used. The emissions are in fact much lower than these limits. By the comparison we also identified the most efficient strategies and the best policies to inform and to involve people. Success in siting an unwanted but needed facility requires that authorities fully involve the public with openness and integrity in all aspects of the planning process. Starting from these result and in order to exploit what is already effective, some proposals where outlined and aim to be the basis for further approaches to design waste disposal plants

Indagine epidemiologica sulla prevalenza di mastiti cliniche in allevamenti bovini italiani

Sono stati valutati 6718 campioni di latte provenienti da un bacino d\u2019utenza comprendente tutto il territorio italiano. Gli animali presentavano manifestazioni cliniche ad uno o pi\uf9 quarti. Sono state effettuate analisi batteriologiche su tutti i campioni al fine di evidenziarne gli agenti eziologici responsabili dell\u2019infiammazion