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Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, prion diseases such as Creutzfeldt–Jakob’s disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer’s disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.

Michele De Tursi,1 Marinella Zilli,1 Consiglia Carella,1 Matteo Auriemma,2 Maria Nadia Lisco,2 Marta Di Nicola,3 Giuseppe Di Martino,4 Clara Natoli,1 Paolo Amerio2 1Department of Medical, Oral and Biotechnological Sciences, Medical Oncology Unit, 2Department of Dermatology and Venereology, 3Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, 4Department of Medicine and Aging Science, University degli Studi “G d’Annunzio” Chieti-Pescara, Chieti, Italy Objectives: The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab. Methods: Cutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman’s rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring. Results: A positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity. Conclusion: There is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system. Keywords: cetuximab, skin toxicity, EGFRI, colorectal cancer, ESS

The aim of this communication is to show how a very simple stagnation plate positioned transversally to the of an air-ethylene premixed flame ([C]/[O]=1.38) does introduce significant changes in both flame temperature, soot 2D distribution and, moreover, does produces a dramatic increase of the soot particle residence time about a factor 6-8 with respect to the identical flame without the stagnation plate. This has crucial effect of the possibility to modulate the permanence time of the carbon particle in the high-reactive flow according to the design of the burner system.

Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc).Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period.Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension.Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.

This paper illustrates the results of an experimental investigation carried out on the liquid fuel spray from a multi-jet common rail injection system both under non evaporative and evaporative conditions. Tests have been taken using a 5 hole, 0.13 mm diameter, 150° spray angle, micro-sac nozzle having a flow rate of 270 cm³/30 sec@10 MPa. The aim of this work is the characterization of the structure of the fuel spray, in terms of global fuel behavior, liquid spray atomization as well velocity and size droplets dispersion. Images of spray evolution have been taken, under non evaporative conditions, injecting the fuel within quiescent inert gas, at different density, in a high-pressure optically-accessible cylindrical vessel with three large quartz windows. Under evaporative conditions, the experiments have been taken within a crank-case scavenged single-cylinder 2-stroke direct injection Diesel engine provided of optical accesses to the combustion chamber. It allows to study the fuel injection process under thermodynamic conditions similar to those currently reached in modern direct injection diesel engines. The air velocity field within the combustion chamber is low enough to assume that the fuel is injected at quiescent conditions, guaranteeing the same fluid flow conditions as those reproduced for tests within the vessel for non evaporative spray conditions. Liquid droplets size and axial velocity profiles have been estimated by applying the phase Doppler anemometry (PDA) technique spraying the fuel with a multiple injection strategy in an optically accessible vessel at ambient temperature and atmospheric pressure under quiescent conditions. PDA tests have been performed at different axial and radial distances from the injector nozzle in order to provide time resolved droplets size and axial velocity at different locations. Fuel droplets size and axial velocity distribution have provided detailed information on the spray morphology evolution, showing a jet structure composed by larger droplets during the transient needle opening and closure phases of the pilot, pre and main injection. During the steady state injection phase, instead, an homogeneous jet structure is highlighted close to the spray axis, with droplets diameter in a range of 1÷5 µm and axial velocity of about 100 m/s. Around the jet periphery an heterogeneous structure composed of droplets having a diameter up to 20 µm traveling at low axial velocity have been observed.

The aim of the present paper is to provide an insight into the fluid dynamic processes that occur during the air/fuel mixture formation period in direct injection diesel engines. An experimental and numerical investigation has been performed to analyze the mixing process between an evaporating diesel spray and a swirl air flow under realistic engine conditions. Experimental tests have been carried out spraying the fuel within an optically accessible prototype 2-stroke diesel engine equipped with an external combustion chamber having cylindrical shape. The intake air flow, coming from the engine cylinder, is forced within the combustion chamber by means of a tangential duct generating a well-structured swirl flow similar to that developing in a real light-duty diesel engine with a high swirl ratio. A micro-sac, 5-hole, 0.13 mm diameter, 150\mD spray angle electro-hydraulic injector supplies the fuel by a common rail injection system able to manage multiple injection strategies. The air/fuel spray interaction for two injection strategies under controlled air swirl levels as well air density and gas temperature has been investigated. The Mie-scattering-based, 2D-imaging technique has provided global information on the spray evolution in terms of liquid spray morphology and tip penetration. The Particle Image Velocimetry (PIV) technique has also been applied to estimate the velocity vector distribution of the liquid fuel droplets. CFD transient analysis has been carried out by the 3-D Star_CD code. The k-\ge turbulence model, Huh-Gosman atomization model and Reitz-Diwaker secondary breakup model have been adopted to predict the fuel spray evolution and its interaction with the swirl flow under the same experimental conditions. The grid, reproducing the geometry of the combustion chamber, has been made using Star_CD tools setting the boundary conditions the same as the experimental ones.

One of the most important phases in the development of direct-injected diesel engines is the optimization of the fuel spray evolution within the combustion chamber, since it strongly influences both the engine performance and the pollutant emissions. Aim of the present paper is to provide information about mixture formation within the combustion chamber of a heavy-duty direct injection (HDDI) diesel engine for marine applications. Spray evolution, in terms of tip penetration, is at first investigated under quiescent conditions, both experimentally and numerically, injecting the fuel in a vessel under ambient temperature and controlled gas back-pressure. Results of penetration and images of the spray from the optically accessible high-pressure vessel are used to investigate the capabilities of some state-of-the-art spray models within the STAR-CD software in correctly capturing spray shape and propagation. The experimental investigation is carried out using a mechanical injection pump equipping a heavy-duty, eight-cylinder engine. Only one of its plungers is activated, and the fuel is discharged through a seven-hole nozzle, 0.40 mm in diameter, mounted on a mechanical injector. Tests are carried out at two different load fuel amounts, representing 50%, and 100% respectively, and results are used as database for the CFD setup. CFD analyses of the intake and compression strokes are at first performed in order to compare two different combustion chambers and different jet orientations with respect to the combustion chamber cavities, running the engine under motored conditions and injecting 50% load fuel amount. Both the two tested pistons show two-stage deep valve pockets hollowed under the valve seats projections, but some relevant differences exist in the piston outer region and in the squish area. Subsequently, full CFD analyses of the intake, compression and combustion processes are performed for the two different combustion chambers and the previously optimized jet orientation, operating the engine at full load, maximum revving speed. Numerical predictions are used to assess the influence of both combustion chamber shapes on the mixture formation effectiveness and the engine-out emissions.

The aim of the present work is to analyze the effect of the injection pressure on the flow pattern and droplets size in a gasoline hollow-cone spray generated by a swirled injector, applying Particle Image Velocimetry (PIV) and Phase Doppler Anemometry (PDA). Experiments were carried out in the range of injection pressures between 6 and 10 Mpa using a common rail injection system, a commercial swirled type injector with a nozzle diameter of 0.50 mm and a cone angle of 67°. The investigation was carried out injecting the fuel in a chamber at ambient temperature and pressure. A 2-D imaging technique was used to follow the global evolution of the spray as function of the injection time in order to estimate the jet development, the morphology of the spray, and the instantaneous velocity field of fuel droplets. PIV images were captured, firstly, aligning the light sheet to the vertical axis of the spray; then, experiments were also taken with the light sheet placed through the cross section of the spray in order to explore the structure and velocity field, at different distances from the nozzle. A PDA system was used to acquire, simultaneously, the droplets velocity as well the droplets size. The system, equipped with an argon-ion laser, was set in forward scattering mode at an off-axis of 30°. Measurements were performed at the same operative conditions as for the visualization ones, choosing different distances from the nozzle. Droplets velocity and size data set provided a minimum of 40,000 in-cycle resolved valid data that were analyzed using the ensemble averaging technique. Results provided detailed information on the spatial velocity distribution and size of droplets close to the nozzle region. Ensemble averaged velocity field of fuel droplets obtained on the vertical plane through the injector axis showed high velocity values up to 100 m/s in the early stage of injection, whereas during the transition to completely developed main spray, droplets travel at lower velocities. The velocity field obtained on the cross section of the spray, at locations close to the nozzle (5 and 10 mm) and in the early stage of injection (up to 0.6 ms), showed a symmetric radial velocity field around the spray axis. Size measurements performed near the nozzle showed a D_ profile constant along the stationary period of injection and not affected by the injection pressure. Results also gave a global increasing trend of the temporally averaged mean diameter along the spray axis.

The present paper aims at providing experimental results on the spray structure and its interaction with the air flow generated by the intake ducts of a commercial light duty gasoline direct injection (GDI) engine head. The investigation was carried out by the Particle Image Velocimetry (PIV) technique to investigate the air flow and fuel droplets velocity evolution within a prototype cylinder with optical accesses. Experiments were carried out at various operating conditions reproducing the mixture preparation for an early injection strategy. The PIV technique was applied in a flow test rig assembled with a blower, which supplied the intake flow rate, connected to the intake manifold of a commercial 4-valve direct injection gasoline engine head modified to lay down an external driving control system for the valves motion. Experiments were taken equipping the engine head with a common rail injection system able to work up to 10 MPa, and a swirled type injector having a nozzle diameter of 0.50 mm and a nominal cone angle of 60°. Tests were taken, on a plane crossing the cylinder and the injector axes, supplying to the prototype cylinder an intake flow rate of 29 m3/h and spraying the gasoline at two injection timings in a range of injection pressure of 6, 8, and 10 MPa. The results provided detailed information on the intake flow field behavior and the evolution of fuel jet within the air flow. The intake flow velocity distribution, acquired at different cam angles during the induction, showed the development of an initial clockwise tumble flow with a tendency to produce two large flow structures: a main counter clockwise vortex and a clockwise ones located at the opposite side of the field of view. Images of the interaction of the fuel with the tumble motion displayed, firstly, a fuel jet shape that traveled not affected by the tumble motion because of its high momentum. Later during the intake, the fuel was strongly distorted by the air motion with the formation of clusters detached from the main jet and spread within the cylinder so allowing to hypothesize that the intake bulk flow may be a crucial parameter to control the fuel penetration and the droplets distribution within the cylinder.

Experimental measurements and numerical computations were made to characterize a spray generated by a high-pressure swirl injector. The Phase Doppler technique was applied to get information on droplet sizes (d10) and axial velocities at defined distances from the injector tip. Global spray visualization was also made. Computations were carried out using a modified version of KIVA 3V. In particular, the break-up length of the sheet and its dimension were computed from a semi-empirical correlation related to the wave instability theory suggested by Dombrowski and Hooper, including the modifications introduced by Han and Reitz. Two different approaches were used to describe the initial spray conditions. According to the first, discrete particles with a characteristic size equal to the thickness of the sheet are injected. The second approach assumes, that the particles having a SMD computed by a semi-empirical correlation are injected according to a statistical distribution. In both cases droplet break-up occurs when the traveling distance becomes greater than the sheet break up length. In addition, in both cases, the secondary break up is based on the TAB model. A simple model based on mass and momentum conservation has been set up to calculate the sheet thickness at nozzle exit and to describe the evolution of axial and tangential components of motion at the start of injection.

An experimental investigation, using the Laser Doppler Anemometry (LDA) technique, was carried out to investigate the complex structure of the intake flow in a commercial four-cylinder automotive desel engine. The attention was focused on the evaluation of the mean motion and turbulence intensity by using a steady state test rig with dynamic valve flow arrangements, supplying a flow rate of 17.4m\u3/h, that corresponds to the actual flow rate of the engine running at 2,000 rpm. The LDA tests were performed with the engine head mounted on a plexiglas cylinder, having the same diameter as that of the real engine, equipped with optical accesses. The intake manifold was connected to a flow bench tester to simulate the actual flow rates of the engine. Measurement points were located within the cylinder at different distances from the cylinder axis, on two orthogonal diameters, and at different depths from the engine head. The instantaneous velocities were processed by using an ensemble averaging technique in order to estimate the mean velocity and the turbulence intensity. The main results showed that both the mean tangential and axial velocities increase during the valve opening period, reaching the maximum magnitude when the valve is closed for every measurement points. The velocities decrease subsequently to near zero values at 60\mD cam angle (c.a.) after the valve closure. Results highlighted a complicated flow field structure with a tumble motion in the vertical plane, which forms and grows during the valve lift and spreads until 60\mD c.a. after the valve closure. The turbulence intensity profile displayed a high level around the valve closure with a decaying trend until 60\mD c.a. after the valve closure.

The present paper aims at investigating the flow field behavior within a reciprocating engine under motoring conditions. Simultaneously two velocity components of the air velocity were acquired at different engine speeds within the cylinder at different radii from the cylinder axis. Mean motion, integral time scales and Reynolds shear stresses, for the radial and tangential components, were estimated from the instantaneous velocity data by applying an ensemble averaging technique. The integral time scale was obtained from the single point time autocorrelation function whereas, the Reynolds shear stresses were computed through the estimate of the degree of the fluctuations correlation. Tests, carried out at 1,000, 1,500, and 2,000 rpm, showed that the tangential mean motion scales approximately with engine speed whereas a radial inward motion can be observed during the last part of compression. The integral time scale shows a global decrease along the compression and an approximate inverse scaling trend with engine speed. Further, an increase of the Reynolds shears stress, at the end of compression, was observed.