Highlights d IGFBP3 peripheral levels are increased in T1D and diabetic enteropathy (DE) d IGFBP3... more Highlights d IGFBP3 peripheral levels are increased in T1D and diabetic enteropathy (DE) d IGFBP3 disrupts CoSCs via a TMEM219-dependent/ caspase-mediated mechanism d Treatment of T1D restores appropriate IGFBP3 peripheral levels and improves DE d The ecto-TMEM219 recombinant protein quenches peripheral IGFBP3 and preserves CoSCs
The Science of the total environment, Jan 15, 2012
The Po Valley in Northern Italy is frequently affected by high PM10 concentrations, where both na... more The Po Valley in Northern Italy is frequently affected by high PM10 concentrations, where both natural and anthropogenic sources play a significant role. To improve air pollution modeling, 3D dust fields, produced by means of the DREAM dust forecasts, were integrated as boundary conditions into the mesoscale 3D deterministic Transport Chemical Aerosol Model (TCAM). A case study of the TCAM and DREAM integration was implemented over Northern Italy for the period May 15-June 30, 2007. First, the Saharan dust impact on PM10 concentration was analyzed for eleven remote PM10 sites with the lowest level of air pollution. These remote sites are the most sensitive to Saharan dust intrusions into Northern Italy, because of the absence of intensive industrial pollution. At these remote sites, the observed maxima in PM10 concentration during dust events is evidence of dust aerosol near the surface in Northern Italy. Comparisons between modeled PM10 concentrations and measurements at 230 PM10 s...
The use of space-borne measurements of trace gas constituents for air quality monitoring is consi... more The use of space-borne measurements of trace gas constituents for air quality monitoring is considerably increased during the past decade. This is due mainly to the new generation sensors able to observe large areas with good temporal resolution and due to new assimilation techniques that allow a synergetic use of information from satellite and from Chemical Transport Models (CTM). In
Secondary atmospheric pollution originates through nonlinear chemical-physical processes involvin... more Secondary atmospheric pollution originates through nonlinear chemical-physical processes involving precursor emissions (VOC -volatile organic compounds, NOxnitrogen oxides, NH3 -ammonia, pPM -primary particulate matter and SOx -sulfur oxides). Exposure to secondary atmospheric pollution can lead to detrimental effects on human health and ecosystems, and so decision makers need support in developing plans to improve air quality, acting in terms of precursor emission reductions. This task is really challenging due to nonlinearities bringing to formation and accumulation of secondary pollution. It is even more difficult when considering at the same time air quality improvement and cost of implementation policies. In the literature the following methodologies, based on Integrated Assessment Modeling, are available to support the design of effective policies: (a) scenario analysis (Thunis et al., 2007), (b) cost-benefit analysis (Rabl et al., 2005) (c) cost-effectiveness analysis (Carslon et al., 2004) and (d) multi-objective analysis (Carnevale et al. 2008, Carnevale et al. 2009).
Exceeding the air quality standards set by the European Union for ground-level concentrations of ... more Exceeding the air quality standards set by the European Union for ground-level concentrations of ozone and PM has significant impact on human health and vegetation. This is a well-known problem in Northern Italy, where high anthropogenic emissions and frequent stagnant meteorological conditions bring to very high concentrations of PM in winter and of ozone in summer. Another peculiarity of the Northern Italy domain is the fact that the non-attainment of secondary pollution standards is not restricted to urban areas but often occurs away from cities, at mesoscale. For this reason, in a scenario analysis framework, it is necessary to evaluate emission control strategies considering accurate deterministic simulations performed with complex modeling systems. Meteorological models are an important part of the deterministic modeling systems. The meteorological variables rule pollutants advection, diffusion, wet deposition, chemical reactions and therefore need to be adequately simulated. Within an HPC-EUROPE (Pan-European Research Infrastructure on High Performance Computing) cooperation project the meteorological conditions over Northern Italy were simulated using RAMS4.4 in parallel mode for the year 2004, creating a database for further air quality assessments. First results of the study and comparisons between modeled and measured meteorological parameters are presented and discussed in the paper.
To control tropospheric ozone Environmental Authorities need to develop air quality plans, implem... more To control tropospheric ozone Environmental Authorities need to develop air quality plans, implementing emission reduction control strategies. This is a challenging task, mainly due to nonlinear processes that bring to ozone formation and accumulation, forced by precursor emissions and solar radiation. This is even more difficult when considering, at the same time, effectiveness and costs of alternative environmental policies. In this study a multi-objective mathematical problem is proposed, considering air quality and cost objectives. Air quality objective is formalized as source-receptor model identified processing simulations of a complex photochemical modelling system. Cost objective is formalized identifying cost functions linking technology cost to emission reduction. The proposed methodology has been applied to a complex domain in Northern Italy, including Milan metropolitan area, a region characterized by high ozone levels during summer season.
Riassunto: Nel pianificare strategie di controllo della qualità dell'aria, le Autorità regionali ... more Riassunto: Nel pianificare strategie di controllo della qualità dell'aria, le Autorità regionali necessitano di strumenti modellistici che consentano di valutare sia l'efficienza, sia i costi di diverse misure di riduzione delle emissioni. Il problema può essere formalizzato come un problema multi-obiettivo che integra modelli sorgente-recettore e modelli di valutazione dei costi di abbattimento degli inquinanti primari. Entrambi gli aspetti presentano elementi di complessità. In questo lavoro la relazione non lineare tra le emissioni dei precursori e le concentrazioni di inquinanti secondariè descritta per mezzo di modelli neuro-fuzzy, calibrati utilizzando i risultati delle simulazioni di lungo termine di un sistema modellistico multifase. Il caso studio preso in esameè la regione Lombardia; quest'area, caratterizzata da orografia complessa, consistenti emissioni urbane ed industriali ed una fitta rete stradale,è frequentemente interessata da episodi critici di inquinamento secondario.
Very high ground level concentrations of PM in winter and of ozone in summer often occur in North... more Very high ground level concentrations of PM in winter and of ozone in summer often occur in Northern Italy, due to the high anthropogenic emissions and frequent stagnant meteorological conditions that characterize the area. These problems are not only related to urban, but also to suburban areas through the entire Po Valley. In such a situation it is important to use deterministic Chemical Transport Models, that allow the evaluation of the effect of different air quality control policies on secondary pollution concentrations. Chemical Transport Models generally are part of more complex deterministic modelling systems, encompassing also emission models, meteorological models, and initial and boundary condition processors. Meteorological models are an important module of deterministic modelling systems and, due to their complexity, require high computational costs to perform simulations. Within the HPC-EUROPA (Pan-European Research Infrastructure on High Performance Computing) cooperation project, that allows the use of clusters of CPUs all around Europe, the meteorological fields over Northern Italy have been simulated using RAMS, creating a database for future air quality assessments.
The design of air quality plans requires the development and the application of Decision Support ... more The design of air quality plans requires the development and the application of Decision Support System (DSS) to assess both the impact of emission reduction strategies on pollution indexes and the costs of such emission reductions. The problem can be formalized as a multi-objective mathematical program, integrating local pollutant-precursor models and the estimate of emission reduction costs. Both aspects present several complex elements. In particular the exposure index can be assessed by means of deterministic complex modelling systems with high computational costs that can't be used during the optimization procedure. The most valuable solution to this issue consists in the identification of neural network models linking precursor emissions and the air quality index starting from the results of a limited number of deterministic model simulations. One of the main points in the identification procedure is the selection of the input and consequently the neural network architecture. In this paper an interactive input selection technique is applied to identify the neural network linking the PM10 (particulate matter with size smaller than 10 µm) concentration to the emission of its precursor. The methodology has been applied to Northern Italy for PM10 exposure control. The results stress that high performance can be obtained with a very limited set of input data both in terms of neural network performances and optimization robustness.
The paper describes a certain number of stochastic predictors of daily and hourly SO2 concentrati... more The paper describes a certain number of stochastic predictors of daily and hourly SO2 concentration in the Venetian Lagoon area. More precisely, the SO1 concentration in each inhabited subarea of the region is represented by the Dosage Area Product (DAP), namely the integral of the daily dosage over each subarea. From each stochastic model a real time predictor is derived. namely a recursive relationship allowing to forecast, at the beginning of each hour or day, the DAP levels in future periods. Moreover, a comparison is made between the performance of predictors using only recorded SO, data and predictors using also meteorological data such as wind directions and speeds, in order to evaluate the inclusion of such meteorological information.
A case of pollution emission and monitoring in an area of northern Italy is considered in this pa... more A case of pollution emission and monitoring in an area of northern Italy is considered in this paper. Specifically, air pollution is due to a point source of SO, (a power plant) while SO, ground concentration measurements are supplied by a network of 23 stations. The paper deafs with the evaluation
Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical pr... more Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental card...
Proceedings of the 48h IEEE Conference on Decision and Control (CDC) held jointly with 2009 28th Chinese Control Conference, 2009
An optimal interpolation technique is formalized and applied to the output of an air quality dete... more An optimal interpolation technique is formalized and applied to the output of an air quality deterministic model in order to improve the description of the evolution of pollutant (namely particulate matter, PM10) in atmosphere. The paper presents an application of the methodology to the Northern Italy region, often affected by high concentration of PM10. The validation of the methodology performed for winter 2004 shows that the re-analysis highly improves the description of the phenomena both in terms of mean error and correlation coefficient.
49th IEEE Conference on Decision and Control (CDC), 2010
Different Data Assimilation techniques have been formalized and applied in the context of complex... more Different Data Assimilation techniques have been formalized and applied in the context of complex nonlinear models, to describe chemistry and physics of the atmosphere. In the literature the main approaches presented are based on a) statistical interpolation (SI) techniques, including optimal interpolation methods, residual kriging methods, regression, etc... and on b) variational methods, as well as ensemble methods such as Ensemble Kalman filters (EnKF). The aim of all these methods is to combine various data sources, to provide an optimal estimate of the spatial distribution of a particular pollutant, considering the uncertainties in the measurements as well as in the models. This paper presents the Ensemble Kalman Filter (EnKF) scheme used to assimilate ozone measurements from ground monitoring stations in the simulations performed by an air quality model system. The Data Assimilation scheme has been applied to Northern Italy. Results show that the methodology highly improves the ozone estimation.
Offline data assimilation analysis applied to TCAM model • Comparison of optimal interpolation an... more Offline data assimilation analysis applied to TCAM model • Comparison of optimal interpolation and Ensemble Kalman Filter performances • Consistency between background TCAM fields and assimilation technique results
Journal of the American Society of Nephrology, 2014
Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted the... more Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted therapies to halt or prevent these complications are currently not available. Here, we show that the immune-related molecule B7-1/CD80 is a critical mediator of podocyte injury in type 2 diabetic nephropathy. We report the induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2 diabetes. Genetic and epidemiologic studies revealed the association of two single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy. Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28 correlated with the progression to ESRD in individuals with type 2 diabetes. In vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase-dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1 in podocytes increased apoptosis and induced disruption of the cytoskeleton that were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was also induced in vivo in two murine models of diabetic nephropathy, and treatment with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney pathology in these animals. Taken together, these results identify B7-1 inhibition as a potential therapeutic strategy for the prevention or treatment of diabetic nephropathy.
Surgical hand disinfection (with an alcohol-based hand rub) and surgical handwash (with an antise... more Surgical hand disinfection (with an alcohol-based hand rub) and surgical handwash (with an antiseptic-based liquid soap) are accepted measures to reduce the risk for surgical site infections. The new European Standards allow a comparison of their antimicrobial efficacy. The bactericidal activity of surgical hand rubs [Sterillium and Softaman, (active ingredient ¼ alcohols)] and handwashes [Derman plus (triclosan), Hibiscrub (chlorhexidine) and Betadine (PVP -iodine)] was tested according to the prEN 12054 suspension test using Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus hirae, and to prEN 12791 for the effect on resident skin flora in comparison with 1-propanol, 60% (v/v). All five products achieved a reduction of test bacteria within 3 min of . 10 5 -fold so fulfilling prEN 12054. However, only Hibiscrub, Sterillium and Softa Man met the requirements of prEN 12791, giving a mean reduction of resident micro-organisms (immediate and sustained effect) which was not significantly lower than the reference alcohol (P . 0.1; Wilcoxon matched-pairs signed-rank test). Sterillium was significantly more effective than the reference alcohol (immediate and sustained affect). Products for surgical hand disinfection may have equal antimicrobial activity in suspension tests but show large differences under practical conditions. Healthcare workers should not rely on results from suspension tests when deciding on a product for surgical hand disinfection.
S U M M A R Y Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid su... more S U M M A R Y Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 a-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells. (J Histochem Cytochem 58:881-889, 2010) K E Y W O R D S carboxyl ester lipase pituitary adenoma localization
Highlights d IGFBP3 peripheral levels are increased in T1D and diabetic enteropathy (DE) d IGFBP3... more Highlights d IGFBP3 peripheral levels are increased in T1D and diabetic enteropathy (DE) d IGFBP3 disrupts CoSCs via a TMEM219-dependent/ caspase-mediated mechanism d Treatment of T1D restores appropriate IGFBP3 peripheral levels and improves DE d The ecto-TMEM219 recombinant protein quenches peripheral IGFBP3 and preserves CoSCs
The Science of the total environment, Jan 15, 2012
The Po Valley in Northern Italy is frequently affected by high PM10 concentrations, where both na... more The Po Valley in Northern Italy is frequently affected by high PM10 concentrations, where both natural and anthropogenic sources play a significant role. To improve air pollution modeling, 3D dust fields, produced by means of the DREAM dust forecasts, were integrated as boundary conditions into the mesoscale 3D deterministic Transport Chemical Aerosol Model (TCAM). A case study of the TCAM and DREAM integration was implemented over Northern Italy for the period May 15-June 30, 2007. First, the Saharan dust impact on PM10 concentration was analyzed for eleven remote PM10 sites with the lowest level of air pollution. These remote sites are the most sensitive to Saharan dust intrusions into Northern Italy, because of the absence of intensive industrial pollution. At these remote sites, the observed maxima in PM10 concentration during dust events is evidence of dust aerosol near the surface in Northern Italy. Comparisons between modeled PM10 concentrations and measurements at 230 PM10 s...
The use of space-borne measurements of trace gas constituents for air quality monitoring is consi... more The use of space-borne measurements of trace gas constituents for air quality monitoring is considerably increased during the past decade. This is due mainly to the new generation sensors able to observe large areas with good temporal resolution and due to new assimilation techniques that allow a synergetic use of information from satellite and from Chemical Transport Models (CTM). In
Secondary atmospheric pollution originates through nonlinear chemical-physical processes involvin... more Secondary atmospheric pollution originates through nonlinear chemical-physical processes involving precursor emissions (VOC -volatile organic compounds, NOxnitrogen oxides, NH3 -ammonia, pPM -primary particulate matter and SOx -sulfur oxides). Exposure to secondary atmospheric pollution can lead to detrimental effects on human health and ecosystems, and so decision makers need support in developing plans to improve air quality, acting in terms of precursor emission reductions. This task is really challenging due to nonlinearities bringing to formation and accumulation of secondary pollution. It is even more difficult when considering at the same time air quality improvement and cost of implementation policies. In the literature the following methodologies, based on Integrated Assessment Modeling, are available to support the design of effective policies: (a) scenario analysis (Thunis et al., 2007), (b) cost-benefit analysis (Rabl et al., 2005) (c) cost-effectiveness analysis (Carslon et al., 2004) and (d) multi-objective analysis (Carnevale et al. 2008, Carnevale et al. 2009).
Exceeding the air quality standards set by the European Union for ground-level concentrations of ... more Exceeding the air quality standards set by the European Union for ground-level concentrations of ozone and PM has significant impact on human health and vegetation. This is a well-known problem in Northern Italy, where high anthropogenic emissions and frequent stagnant meteorological conditions bring to very high concentrations of PM in winter and of ozone in summer. Another peculiarity of the Northern Italy domain is the fact that the non-attainment of secondary pollution standards is not restricted to urban areas but often occurs away from cities, at mesoscale. For this reason, in a scenario analysis framework, it is necessary to evaluate emission control strategies considering accurate deterministic simulations performed with complex modeling systems. Meteorological models are an important part of the deterministic modeling systems. The meteorological variables rule pollutants advection, diffusion, wet deposition, chemical reactions and therefore need to be adequately simulated. Within an HPC-EUROPE (Pan-European Research Infrastructure on High Performance Computing) cooperation project the meteorological conditions over Northern Italy were simulated using RAMS4.4 in parallel mode for the year 2004, creating a database for further air quality assessments. First results of the study and comparisons between modeled and measured meteorological parameters are presented and discussed in the paper.
To control tropospheric ozone Environmental Authorities need to develop air quality plans, implem... more To control tropospheric ozone Environmental Authorities need to develop air quality plans, implementing emission reduction control strategies. This is a challenging task, mainly due to nonlinear processes that bring to ozone formation and accumulation, forced by precursor emissions and solar radiation. This is even more difficult when considering, at the same time, effectiveness and costs of alternative environmental policies. In this study a multi-objective mathematical problem is proposed, considering air quality and cost objectives. Air quality objective is formalized as source-receptor model identified processing simulations of a complex photochemical modelling system. Cost objective is formalized identifying cost functions linking technology cost to emission reduction. The proposed methodology has been applied to a complex domain in Northern Italy, including Milan metropolitan area, a region characterized by high ozone levels during summer season.
Riassunto: Nel pianificare strategie di controllo della qualità dell'aria, le Autorità regionali ... more Riassunto: Nel pianificare strategie di controllo della qualità dell'aria, le Autorità regionali necessitano di strumenti modellistici che consentano di valutare sia l'efficienza, sia i costi di diverse misure di riduzione delle emissioni. Il problema può essere formalizzato come un problema multi-obiettivo che integra modelli sorgente-recettore e modelli di valutazione dei costi di abbattimento degli inquinanti primari. Entrambi gli aspetti presentano elementi di complessità. In questo lavoro la relazione non lineare tra le emissioni dei precursori e le concentrazioni di inquinanti secondariè descritta per mezzo di modelli neuro-fuzzy, calibrati utilizzando i risultati delle simulazioni di lungo termine di un sistema modellistico multifase. Il caso studio preso in esameè la regione Lombardia; quest'area, caratterizzata da orografia complessa, consistenti emissioni urbane ed industriali ed una fitta rete stradale,è frequentemente interessata da episodi critici di inquinamento secondario.
Very high ground level concentrations of PM in winter and of ozone in summer often occur in North... more Very high ground level concentrations of PM in winter and of ozone in summer often occur in Northern Italy, due to the high anthropogenic emissions and frequent stagnant meteorological conditions that characterize the area. These problems are not only related to urban, but also to suburban areas through the entire Po Valley. In such a situation it is important to use deterministic Chemical Transport Models, that allow the evaluation of the effect of different air quality control policies on secondary pollution concentrations. Chemical Transport Models generally are part of more complex deterministic modelling systems, encompassing also emission models, meteorological models, and initial and boundary condition processors. Meteorological models are an important module of deterministic modelling systems and, due to their complexity, require high computational costs to perform simulations. Within the HPC-EUROPA (Pan-European Research Infrastructure on High Performance Computing) cooperation project, that allows the use of clusters of CPUs all around Europe, the meteorological fields over Northern Italy have been simulated using RAMS, creating a database for future air quality assessments.
The design of air quality plans requires the development and the application of Decision Support ... more The design of air quality plans requires the development and the application of Decision Support System (DSS) to assess both the impact of emission reduction strategies on pollution indexes and the costs of such emission reductions. The problem can be formalized as a multi-objective mathematical program, integrating local pollutant-precursor models and the estimate of emission reduction costs. Both aspects present several complex elements. In particular the exposure index can be assessed by means of deterministic complex modelling systems with high computational costs that can't be used during the optimization procedure. The most valuable solution to this issue consists in the identification of neural network models linking precursor emissions and the air quality index starting from the results of a limited number of deterministic model simulations. One of the main points in the identification procedure is the selection of the input and consequently the neural network architecture. In this paper an interactive input selection technique is applied to identify the neural network linking the PM10 (particulate matter with size smaller than 10 µm) concentration to the emission of its precursor. The methodology has been applied to Northern Italy for PM10 exposure control. The results stress that high performance can be obtained with a very limited set of input data both in terms of neural network performances and optimization robustness.
The paper describes a certain number of stochastic predictors of daily and hourly SO2 concentrati... more The paper describes a certain number of stochastic predictors of daily and hourly SO2 concentration in the Venetian Lagoon area. More precisely, the SO1 concentration in each inhabited subarea of the region is represented by the Dosage Area Product (DAP), namely the integral of the daily dosage over each subarea. From each stochastic model a real time predictor is derived. namely a recursive relationship allowing to forecast, at the beginning of each hour or day, the DAP levels in future periods. Moreover, a comparison is made between the performance of predictors using only recorded SO, data and predictors using also meteorological data such as wind directions and speeds, in order to evaluate the inclusion of such meteorological information.
A case of pollution emission and monitoring in an area of northern Italy is considered in this pa... more A case of pollution emission and monitoring in an area of northern Italy is considered in this paper. Specifically, air pollution is due to a point source of SO, (a power plant) while SO, ground concentration measurements are supplied by a network of 23 stations. The paper deafs with the evaluation
Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical pr... more Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental card...
Proceedings of the 48h IEEE Conference on Decision and Control (CDC) held jointly with 2009 28th Chinese Control Conference, 2009
An optimal interpolation technique is formalized and applied to the output of an air quality dete... more An optimal interpolation technique is formalized and applied to the output of an air quality deterministic model in order to improve the description of the evolution of pollutant (namely particulate matter, PM10) in atmosphere. The paper presents an application of the methodology to the Northern Italy region, often affected by high concentration of PM10. The validation of the methodology performed for winter 2004 shows that the re-analysis highly improves the description of the phenomena both in terms of mean error and correlation coefficient.
49th IEEE Conference on Decision and Control (CDC), 2010
Different Data Assimilation techniques have been formalized and applied in the context of complex... more Different Data Assimilation techniques have been formalized and applied in the context of complex nonlinear models, to describe chemistry and physics of the atmosphere. In the literature the main approaches presented are based on a) statistical interpolation (SI) techniques, including optimal interpolation methods, residual kriging methods, regression, etc... and on b) variational methods, as well as ensemble methods such as Ensemble Kalman filters (EnKF). The aim of all these methods is to combine various data sources, to provide an optimal estimate of the spatial distribution of a particular pollutant, considering the uncertainties in the measurements as well as in the models. This paper presents the Ensemble Kalman Filter (EnKF) scheme used to assimilate ozone measurements from ground monitoring stations in the simulations performed by an air quality model system. The Data Assimilation scheme has been applied to Northern Italy. Results show that the methodology highly improves the ozone estimation.
Offline data assimilation analysis applied to TCAM model • Comparison of optimal interpolation an... more Offline data assimilation analysis applied to TCAM model • Comparison of optimal interpolation and Ensemble Kalman Filter performances • Consistency between background TCAM fields and assimilation technique results
Journal of the American Society of Nephrology, 2014
Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted the... more Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted therapies to halt or prevent these complications are currently not available. Here, we show that the immune-related molecule B7-1/CD80 is a critical mediator of podocyte injury in type 2 diabetic nephropathy. We report the induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2 diabetes. Genetic and epidemiologic studies revealed the association of two single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy. Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28 correlated with the progression to ESRD in individuals with type 2 diabetes. In vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase-dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1 in podocytes increased apoptosis and induced disruption of the cytoskeleton that were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was also induced in vivo in two murine models of diabetic nephropathy, and treatment with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney pathology in these animals. Taken together, these results identify B7-1 inhibition as a potential therapeutic strategy for the prevention or treatment of diabetic nephropathy.
Surgical hand disinfection (with an alcohol-based hand rub) and surgical handwash (with an antise... more Surgical hand disinfection (with an alcohol-based hand rub) and surgical handwash (with an antiseptic-based liquid soap) are accepted measures to reduce the risk for surgical site infections. The new European Standards allow a comparison of their antimicrobial efficacy. The bactericidal activity of surgical hand rubs [Sterillium and Softaman, (active ingredient ¼ alcohols)] and handwashes [Derman plus (triclosan), Hibiscrub (chlorhexidine) and Betadine (PVP -iodine)] was tested according to the prEN 12054 suspension test using Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus hirae, and to prEN 12791 for the effect on resident skin flora in comparison with 1-propanol, 60% (v/v). All five products achieved a reduction of test bacteria within 3 min of . 10 5 -fold so fulfilling prEN 12054. However, only Hibiscrub, Sterillium and Softa Man met the requirements of prEN 12791, giving a mean reduction of resident micro-organisms (immediate and sustained effect) which was not significantly lower than the reference alcohol (P . 0.1; Wilcoxon matched-pairs signed-rank test). Sterillium was significantly more effective than the reference alcohol (immediate and sustained affect). Products for surgical hand disinfection may have equal antimicrobial activity in suspension tests but show large differences under practical conditions. Healthcare workers should not rely on results from suspension tests when deciding on a product for surgical hand disinfection.
S U M M A R Y Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid su... more S U M M A R Y Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 a-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells. (J Histochem Cytochem 58:881-889, 2010) K E Y W O R D S carboxyl ester lipase pituitary adenoma localization
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