1,968 research outputs found

    L'esperienza di decentramento istituzionale in Italia e lo sviluppo locale

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    Il paper rappresenta un primo passo verso una riflessione organica sul tema del decentramento istituzionale in relazione al problema dello sviluppo locale in un’ottica temporale di lungo periodo (partendo cioè dall’unificazione del Regno d’Italia) e intreccia tra loro più piani di analisi: dalle vicende che riguardano gli assetti istituzionali della nazione (sospesi costantemente all’interno del dibattito tra accentramento e decentramento) a quelle che riguardano invece la concreta attività degli enti politici periferici. L’analisi mostra come all’interno di un quadro istituzionale storicamente caratterizzato da un forte accentramento statale, emergano tuttavia i fili di una costante ricerca di protagonismo da parte delle istituzioni politiche locali, le quali, in modo particolare sebbene non esclusivo negli anni repubblicani, “forzano” i limiti normativi dei propri spazi di intervento, facendosi carico direttamente – seppure con intensità e modalità differenti nelle diverse aree territoriali del paese – dei problemi dello sviluppo economico locale.

    High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids

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    The identification of effective biomarkers for early diagnosis, prognosis, and response to treatments remains a challenge in ovarian cancer (OC) research. Here, we present an unbiased high-throughput approach to profile ascitic fluid autoantibodies in order to obtain a tumor-specific antigen signature in OC. We first reported the reactivity of immunoglobulins (Igs) purified from OC patient ascites towards two different OC cell lines. Using a discovery set of Igs, we selected tumor-specific antigens from a phage display cDNA library. After biopanning, 700 proteins were expressed as fusion protein and used in protein array to enable large-scale immunoscreening with independent sets of cancer and noncancerous control. Finally, the selected antigens were validated by ELISA. The initial screening identified eight antigenic clones: CREB3, MRPL46, EXOSC10, BCOR, HMGN2, HIP1R, OLFM4, and KIAA1755. These antigens were all validated by ELISA in a study involving ascitic Igs from 153 patients (69 with OC, 34 with other cancers and 50 without cancer), with CREB3 showing the highest sensitivity (86.95%) and specificity (98%). Notably, we were able to identify an association between the tumor-associated (TA) antibody response and the response to a first-line tumor treatment (platinum-based chemotherapy). A stronger association was found by combining three antigens (BCOR, CREB3, and MRLP46) as a single antibody signature. Measurement of an ascitic fluid antibody response to multiple TA antigens may aid in the identification of new prognostic signatures in OC patients and shift attention to new potentially relevant targets

    Anti-atherogenic modification of serum lipoprotein function in patients with rheumatoid arthritis after tocilizumab treatment, a pilot study

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    Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Patients with RA (n = 8) were studied before and after 4 and 12 weeks of tocilizumab treatment. CLC was measured by a fluorimetric assay of intracellular cholesterol content in human macrophages and CEC was measured for the three main pathways, mediated by the transporters Scavenger Receptor class B-type I (SR-BI), ATP binding cassette-G1 (ABCG1) and-A1 (ABCA1) in specific cell models. After 12 weeks of tocilizumab treatment, serum LDL cholesterol levels were increased, while CLC was reduced. HDL cholesterol levels were unchanged, but CEC was significantly ameliorated for the SR-BI and ABCG1 pathways with respect to baseline. Tocilizumab reduces LDL pro-atherogenic potential despite increasing their serum levels and increases HDL protective activity in RA. The data of our pilot study suggest that tocilizumab regulates lipoprotein function in selected patient populations and lay the groundwork for future larger studies

    Patterns of novel alleles and genotype/phenotype correlations resulting from the analysis of 108 previously undetected mutations in patients affected by neurofibromatosis type I

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    Neurofibromatosis type I, a genetic disorder due to mutations in the NF1 gene, is characterized by a high mutation rate (about 50% of the cases are de novo) but, with the exception of whole gene deletions associated with a more severe phenotype, no specific hotspots and few solid genotype/phenotype correlations. After retrospectively re-evaluating all NF1 gene variants found in the diagnostic activity, we studied 108 patients affected by neurofibromatosis type I who harbored mutations that had not been previously reported in the international databases, with the aim of analyzing their type and distribution along the gene and of correlating them with the phenotypic features of the affected patients. Out of the 108 previously unreported variants, 14 were inherited by one of the affected parents and 94 were de novo. Twenty-nine (26.9%) mutations were of uncertain significance, whereas 79 (73.2%) were predicted as pathogenic or probably pathogenic. No differential distribution in the exons or in the protein domains was observed and no statistically significant genotype/phenotype correlation was found, confirming previous evidences

    Current status of Melcor 2.2 for fusion safety analyses

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    MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of the USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs that emerged from the safety analyses of fusion-related installations has been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgment of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications
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