Verifying the Interplay of Authorization Policies and Workflow in Service-Oriented Architectures (Full version)

A widespread design approach in distributed applications based on the service-oriented paradigm, such as web-services, consists of clearly separating the enforcement of authorization policies and the workflow of the applications, so that the interplay between the policy level and the workflow level is abstracted away. While such an approach is attractive because it is quite simple and permits one to reason about crucial properties of the policies under consideration, it does not provide the right level of abstraction to specify and reason about the way the workflow may interfere with the policies, and vice versa. For example, the creation of a certificate as a side effect of a workflow operation may enable a policy rule to fire and grant access to a certain resource; without executing the operation, the policy rule should remain inactive. Similarly, policy queries may be used as guards for workflow transitions. In this paper, we present a two-level formal verification framework to overcome these problems and formally reason about the interplay of authorization policies and workflow in service-oriented architectures. This allows us to define and investigate some verification problems for SO applications and give sufficient conditions for their decidability.Comment: 16 pages, 4 figures, full version of paper at Symposium on Secure Computing (SecureCom09

Thermoconvective instability and local thermal non-equilibrium in a porous layer with isoflux-isothermal boundary conditions

The effects of lack of local thermal equilibrium between the solid phase and the fluid phase are taken into account for the convective stability analysis of a horizontal porous layer. The layer is bounded by a pair of plane parallel walls which are impermeable and such that the lower wall is subject to a uniform flux heating, while the upper wall is isothermal. The local thermal non-equilibrium is modelled through a two-temperature formulation of the energy exchange between the phases, resulting in a pair of local energy balance equations: one for each phase. Small-amplitude disturbances of the basic rest state are envisaged to test the stability. Then, the standard normal mode procedure is adopted to detect the onset conditions of convective rolls. Beyond the Darcy-Rayleigh number, playing the role of order parameter for the transition to instability, the relevant dimensionless parameters are the inter-phase heat transfer parameter and the thermal conductivity ratio. The disturbance governing equations, formulated as an eigenvalue problem, are solved numerically by a shooting method. Results are reported for the neutral stability curves and for the critical values for the onset of instability

Gill's problem in a sandwiched porous slab

The classical Gill's stability problem for the stationary and parallel buoyant flow in a vertical porous slab with impermeable and isothermal boundaries kept at different temperatures is reconsidered in a different perspective. A three-layer slab is studied instead of a homogeneous slab as in Gill's problem. The three layers have a symmetric configuration where the two external layers have a high thermal conductivity, while the core layer has a much lower conductivity. A simplified model is set up where the thermal conductivity ratio between the external layers and the internal core is assumed as infinite. It is shown that a flow instability in the sandwiched porous slab may arise with a sufficiently large Rayleigh number. It is also demonstrated that this instability coincides with that predicted in a previous analysis for a homogeneous porous layer with permeable boundaries, by considering the limiting case where the permeability of the external layers is much larger than that of the core layer

Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2

Abstract Background: Poly(ADP-Ribose) polymerase (PARP) activity has been demonstrated fundamental in many cellular processes, including DNA repair, cell proliferation and differentiation. In particular, PARP activity has been recently found to affect proliferation, migration, and tube formation of human umbilical vein endothelial cells. In recent times, PARP inhibitors have entered in clinical trials to potentiate cancer treatments by preventing DNA repair, but little is known about the effects performed by different drug concentrations on neoangiogenesis, an essential step in tumor growth. Methods: Human umbilical vein endothelial cells were treated with 3 aminobenzamide (3ABA), a PARP inhibitor, and tested for several different cellular parameters. Results: Here we present in vitro evidence that a low concentration of 3ABA (50 μM), stimulates angiogenesis by decreasing fibrinolytic activity, carried out by urokinase-type plasminogen activator (uPA), and by enhancing matrix metalloprotease-2 (MMP-2) gelatinolytic activity, in fibroblast growth factor-2-stimulated endothelial cells. These unbalanced pathways modify in vitro angiogenic steps, inhibiting chemoinvasion and stimulating tubulogenic activity. Conclusions: Our results suggest that the proangiogenic effect of low concentrations of 3ABA alerts on the efficacy of PARP inhibitors to potentiate anticancer therapy. Moreover, they indicate that endothelial chemoinvasion and tubulogenesis depend on distinct proteolytic pathways

La mobilità sostenibile nelle smart city: Prospettive, sfide e soluzioni

Le città di tutto il mondo affrontano sfide crescenti in termini di congestione del traffico, inquinamento atmosferico e cambiamenti climatici. La smart mobility è emersa come una risposta cruciale a queste sfide, e le smart city offrono un terreno fertile per l'innovazione in questo settore. Questo studio si propone di esaminare il ruolo della mobilità sostenibile nelle smart city, analizzando prospettive, sfide e soluzioni. Cities around the world face growing challenges in terms of traffic congestion, air pollution and climate change. Smart mobility has emerged as a crucial response to these challenges, and smart cities offer fertile ground for innovation in this area. This study aims to examine the role of sustainable mobility in smart cities, analysing perspectives, challenges and solutions

Effect of Acute Ingestion of Green Tea Extract and Lemon Juice on Oxidative Stress and Lipid Profile in Pigs Fed a High-Fat Diet.

Green tea and its catechins have been shown to ameliorate high fat diet-induced oxidative stress and hyperlipidemia. However, low bioavailability of catechins limits their therapeutic potential. Lemon juice (LJ) has been suggested to enhance the bioavailability of catechins in vitro. This study investigated the antioxidative and hypolipidemic efficacy of a single dose of green tea extract (GTE) or GTE plus LJ (GTE + LJ) in high-fat diet fed pigs. Sixteen pigs ingested a single dose of GTE (190 mg/kg/day) or GTE + LJ (0.75 mL/kg/day) mixed with low-fat (LF; 5% fat) or high-fat (HF; 22% fat) diets and blood samples were collected for 24 h. Plasma catechin level peaked at two hours, and gradually returned to baseline after six hours following the intake. The addition of LJ significantly increased plasma catechin level. The diet containing GTE did not lower plasma cholesterol and triacylglycerol (TG) concentrations, superoxide dismutase (SOD) and catalase activity, or malondialdehyde concentration in 24 h in HF-fed pigs. Addition of a single dose of LJ, however, significantly decreased plasma TG level in LF groups but did not cause further changes on any other markers compared to the GTE alone. Our findings indicate limited effect of a single meal containing GTE on plasma antioxidant enzymes, lipid profile, and lipid peroxidation in pigs and no significant synergistic/additive action of adding LJ to GTE within 24 h in pigs. A study with a longer treatment period is warranted to further understand the potential role of GTE in reducing HF diet-induced oxidative stress and the possible synergistic role of LJ

Role of G Protein-coupled Receptor Kinase 4 and β-Arrestin 1 in Agonist-stimulated Metabotropic Glutamate Receptor 1 Internalization and Activation of Mitogen-activated Protein Kinases

The metabotropic glutamate 1 (mGlu(1)) receptor in cerebellar Purkinje cells plays a key role in motor learning and motor coordination. Here we show that the G protein-coupled receptor kinases (GRK) 2 and 4, which are expressed in these cells, regulate the mGlu(1) receptor by at least in part different mechanisms. Using kinase-dead mutants in HEK293 cells, we found that GRK4, but not GRK2, needs the intact kinase activity to desensitize the mGlu(1) receptor, whereas GRK2, but not GRK4, can interact with and regulate directly the activated Galpha(q). In cells transfected with GRK4 and exposed to agonist, beta-arrestin was first recruited to plasma membranes, where it was co-localized with the mGlu(1) receptor, and then internalized in vesicles. The receptor was also internalized but in different vesicles. The expression of beta-arrestin V53D dominant negative mutant, which did not affect the mGlu(1) receptor internalization, reduced by 70-80% the stimulation of mitogen-activated protein (MAP) kinase activation by the mGlu(1) receptor. The agonist-stimulated differential sorting of the mGlu(1) receptor and beta-arrestin as well as the activation of MAP kinases by mGlu(1) agonist was confirmed in cultured cerebellar Purkinje cells. A major involvement of GRK4 and of beta-arrestin in agonist-dependent receptor internalization and MAP kinase activation, respectively, was documented in cerebellar Purkinje cells using an antisense treatment to knock down GRK4 and expressing beta-arrestin V53D dominant negative mutant by an adenovirus vector. We conclude that GRK2 and GRK4 regulate the mGlu(1) receptor by different mechanisms and that beta-arrestin is directly involved in glutamate-stimulated MAP kinase activation by acting as a signaling molecule

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study

Aims: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. Methods: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. Results: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. Conclusions: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response