La cartolarizzazione dei crediti tributari degli enti locali: alcune questioni aperte

Nell\u2019ambito delle operazioni di cartolarizzazione aventi ad oggetto crediti della pubblica amministrazione, una delle questioni interpretative pi\uf9 delicate e tuttora aperte concerne la disciplina applicabile ai fini dell\u2019individuazione dei contraenti coinvolti, ed in particolare del soggetto incaricato di assumere la veste di societ\ue0 veicolo. Alla complessit\ue0 della questione non sembrerebbe, sino ad ora, essersi accompagnata un\u2019approfondita riflessione dottrinale e giurisprudenziale sul tema, nonostante le evidenti ricadute applicative allo stesso connesse. Le successive considerazioni, pur riferite al limitato ambito della cartolarizzazione dei crediti tributari degli enti locali, scaturiscono dal tentativo di affrontare il problema in chiave sistematica, nell\u2019ambito del pi\uf9 generale quadro normativo in materia di appalti pubblici, oltre che della disciplina della cartolarizzazione dei credit

Oxidative potential associated with urban aerosol deposited into the respiratory system and relevant elemental and ionic fraction contributions

Size-segregated aerosol measurements were carried out at an urban and at an industrial site. Soluble and insoluble fractions of elements and inorganic ions were determined. Oxidative potential (OP) was assessed on the soluble fraction of Particulate Matter (PM) by ascorbic acid (AA), dichlorofluorescein (DCFH) and dithiothreitol (DTT) assays. Size resolved elemental, ion and OP doses in the head (H), tracheobronchial (TB) and alveolar (Al) regions were estimated using the Multiple-Path Particle Dosimetry (MPPD) model. The total aerosol respiratory doses due to brake and soil resuspension emissions were higher at the urban than at the industrial site. On the contrary, the doses of anthropic combustion tracers were generally higher at the industrial site. In general, the insoluble fraction was more abundantly distributed in the coarse than in the fine mode and vice versa for the soluble fraction. Consequently, for the latter, the percent of the total respiratory dose deposited in TB and Al regions increased. Oxidative potential assay (OPAA) doses were distributed in the coarse region; therefore, their major contribution was in the H region. The contribution in the TB and Al regions increased for OPDTT and OPDCFH

Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction

For over a century, there has been intense debate as to the reason why some cardiac stresses are pathological and others are physiological. One long-standing theory is that physiological overloads such as exercise are intermittent, while pathological overloads such as hypertension are chronic. In this study, we hypothesized that the nature of the stress on the heart, rather than its duration, is the key determinant of the maladaptive phenotype. To test this, we applied intermittent pressure overload on the hearts of mice and tested the roles of duration and nature of the stress on the development of cardiac failure. Despite a mild hypertrophic response, preserved systolic function, and a favorable fetal gene expression profile, hearts exposed to intermittent pressure overload displayed pathological features. Importantly, intermittent pressure overload caused diastolic dysfunction, altered β-adrenergic receptor (βAR) function, and vascular rarefaction before the development of cardiac hypertrophy, which were largely normalized by preventing the recruitment of PI3K by βAR kinase 1 to ligand-activated receptors. Thus stress-induced activation of pathogenic signaling pathways, not the duration of stress or the hypertrophic growth per se, is the molecular trigger of cardiac dysfunction

Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control

Aggregation of α-synuclein and formation of inclusions are hallmarks of Parkinson's disease (PD). Aggregate formation is affected by cellular environment, but it has been studied almost exclusively in cell-free systems. We quantitatively analyzed α-synuclein inclusion formation and clearance in a yeast cell model of PD expressing either wild-type (WT) α-synuclein or the disease-associated A53T mutant from the galactose (Gal)-inducible promoter. A computer-controlled microfluidics device regulated α-synuclein in cells by means of closed-loop feedback control. We demonstrated that inclusion formation is strictly concentration dependent and that the aggregation threshold of the A53T mutant is about half of the WT α-synuclein (56%). We chemically modulated the proteasomal and autophagic pathways and demonstrated that autophagy is the main determinant of A53T α-synuclein inclusions’ clearance. In addition to proposing a technology to overcome current limitations in dynamically regulating protein expression levels, our results contribute to the biology of PD and have relevance for therapeutic applications

Qualitative and quantitative determination of water in airborne particulate matter

Abstract. This paper describes the optimization and validation of a new simple method for the quantitative determination of water in atmospheric particulate matter (PM). The analyses are performed by using a coulometric Karl-Fisher system equipped with a controlled heating device; different water contributions are separated by the application of an optimized thermal ramp (three heating steps: 50–120 °C, 120–180 °C, 180–250 °C). The analytical performance of the method was verified by using standard materials containing 5.55% and 1% by weight of water. The recovery was greater than 95%; the detection limit was about 20 μg. The method was then applied to NIST Reference Materials (NIST1649a, urban particulate matter) and to real PM10 samples collected in different geographical areas. In all cases the repeatability was satisfactory (10–15%). When analyzing the Reference Material, the separation of four different types of water was obtained. In real PM10 samples the amount of water and its thermal profile differed as a function of the chemical composition of the dust. Mass percentages of 3–4% of water were obtained in most samples, but values up to about 15% were reached in areas where the chemical composition of PM is dominated by secondary inorganic ions and organic matter. High percentages of water were also observed in areas where PM is characterized by the presence of desert dust. A possible identification of the quality of water released from the samples was tried by applying the method to some hygroscopic compounds that are likely contained in PM (pure SiO2, Al2O3, ammonium salts, carbohydrates and dicarboxylic acids) and by comparing the results with those obtained from field samples

Effects of balloon injury on neointimal hyperplasia in steptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals

Ciliated hepatic foregut cyst: A report of 6 cases and a review of the English literature

BACKGROUND: Ciliated hepatic foregut cyst (CHFC) is a rare cystic lesion most commonly identified in segment 4 of the liver that arises from the embryonic foregut. The classic histologic pattern is comprised of 4 distinct layers (inner ciliated epithelial lining, smooth muscle, loose connective tissue, fibrous capsule). Although rare, cases of metaplastic and malignant epithelial lining have been described in CHFC. METHODS: We report 6 additional cases of CHFC, one of which had gastric metaplasia of the cyst lining, and review all reported cases of CHFC in the English literature. We describe the clinicopathologic analysis of 6 cases, with selective immunohistochemical analysis on 1 case with gastric metaplasia. RESULTS: Cases occurred in 4 women and 2 men (average age 55 years, range 42 to 67 years). Cysts ranged in size from 0.7 to 17 cm (average 7.2 cm) and were grossly tan-pink to white with blood-filled contents. The majority were located in segment 4 of the liver, however 2 were located in the porta hepatis. Tumor serologies (CA19-9 and/or CEA) were performed in 3 cases; 1 case demonstrated elevated CA19-9, and 2 cases had laboratory values within normal limits. All cases showed the classic histologic findings, however one case additionally had extensive gastric metaplasia. CONCLUSIONS: In conclusion, CHFC is a rare diagnostic entity that should be considered in the differential diagnosis for cystic hepatic lesions, particularly those located in segment 4 of the liver. Metaplasia and squamous carcinoma can occur, therefore complete surgical excision is the recommended treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13000-015-0321-1) contains supplementary material, which is available to authorized users

MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation

Competition for intracellular resources, also known as gene expression burden, induces coupling between independently co-expressed genes, a detrimental effect on predictability and reliability of gene circuits in mammalian cells. We recently showed that microRNA (miRNA)-mediated target downregulation correlates with the upregulation of a co-expressed gene, and by exploiting miRNAs-based incoherent-feed-forward loops (iFFLs) we stabilise a gene of interest against burden. Considering these findings, we speculate that miRNA-mediated gene downregulation causes cellular resource redistribution. Despite the extensive use of miRNA in synthetic circuits regulation, this indirect effect was never reported before. Here we developed a synthetic genetic system that embeds miRNA regulation, and a mathematical model, MIRELLA, to unravel the miRNA (MI) RolE on intracellular resource aLLocAtion. We report that the link between miRNA-gene downregulation and independent genes upregulation is a result of the concerted action of ribosome redistribution and ‘queueing-effect’ on the RNA degradation pathway. Taken together, our results provide for the first time insights into the hidden regulatory interaction of miRNA-based synthetic networks, potentially relevant also in endogenous gene regulation. Our observations allow to define rules for complexity- and context-aware design of genetic circuits, in which transgenes co-expression can be modulated by tuning resource availability via number and location of miRNA target sites