1,721,201 research outputs found
Development of new therapies against the influenza types A viruses, based on small RNAs targeting the genome regions which codify viral polimerasi.
Convegno di Presentazione Attività di ricerca dei Dottorandi del XXVII Ciclo (II anno di corso) MacroArea 2-Scienze della Vit
Sviluppo di un approccio terapeutico basato su piccoli rna diretti verso i segmenti genomici codificanti la polimerasi del virus dell'influenza
Influenza A viruses, capable of infecting humans and birds, are associated not only to seasonal epidemics, but also to pandemics, with an high impact on Public Health. The emergence of influenza viruses to the currently available drugs and the lack of universal vaccination strategies are main human and veterinarian concerns. Thus, the research of innovative targets for the development of therapeutic anti-influenza A virus strategies is still required. The aim of this study was to develop an innovative antiviral approach based on the delivery into eukaryotic cells susceptible to influenza virus infection of small RNA molecules targeting the highly conserved regions mapping at the 5’ ends of the 3 viral genomic segments encoding for the polymerase (PA, PB1, PB2), an enzyme essential for viral replication (Giannecchini S. et al., 2009- 2011). The target sequences represent the packaging signals of these 3 genomic segments and play an important role during the assembly and budding of the newly formed particles (Qinshan Gao et al., 2012).
To this end, we developed different lentiviral vectors expressing miRNAs [pLenti6/V5-GW/EmGFP-miR] or antisense-RNAs [pLentilox 3.7 GFP] targeting PA, PB1 and PB2 segments. Recombinant lentiviral particles, produced by transfecting human embryonic kidney cells (293T) with both vectors in combination with a packaging systems, were harvested and titrated on human alveolar adenocarcinoma cell line (A549) by FACS analysis. The lentiviral vectors transduction efficiency on different cell lines was evaluated by FACS assay and by quantitative Real-Time PCR. The transduced cells were infected with epidemiologically relevant human influenza viruses type A and B and avian viruses type A. The viral inhibitory activity was assessed by employing an infectivity assay.
We showed that recombinant lentiviral particles expressing miRNA or antisense-RNAs efficiently transduced A549 cell lines that are highly susceptible to influenza virus replication. More importantly, a reduction from 1 to 3 logatims of the viral titre was obtained in all tested cell lines infected with human and avian subtypes of influenza type A viruses. By contrast, no inhibition of influenza type B virus was observed. Furthermore, mutations within the target sequences abolished the antiviral effects of the developed vectors, thus confirming the specificity of the approach. Our study contributes to the demonstration that the expression of small RNAs targeting the packaging signal of the polymerases gene might represent an efficient strategy against the influenza A virus infection in human (especially in pandemic events) and birds
Thermo-Hydrodynamic Analysis of Plain and Tilting Pad Bearings
The demand for higher efficiency and increased equipment compactness is pushing industrial compressors’ designers towards the choice of higher rotor peripheral speed. As a consequence, modern bearing-rotor systems are subject to complex thermal phenomena inducing a renewed interest on their real working conditions. This work is about the validation of the in-house numerical code TILTPAD developed at the Department of Industrial Engineering of the University of Florence for the thermo-hydrodynamic analysis of both plain and tilting pad journal bearings performance. TILTPAD is a steady-state code based on a 2D thin-film approach able to find either the resulting hydrodynamic load using the shaft equilibrium position and the rotational speed (i.e., direct problem) or the shaft equilibrium position once the load and the rotational speed are prescribed (i.e., inverse problem). In order to calculate pads’ pressure distribution a finite element approach is used to solve the Reynolds equation together with a mixed procedure to evaluate pads equilibrium positions. Two steady-state energy equations based on a Petroff-type simplification are implemented in the code. The first one is proposed in the work of Balbahadur and Kirk [1] while the second one is based on an improved mixing model and a temperature dependent viscosity. An iterative procedure is used between Reynolds and energy equations to account for the dependence of the dynamic viscosity on the temperature field. Super-laminar flow regimes are also modeled in the code by means of a simplified approach able to represents, with reasonable accuracy, the effects of Taylor-Couette vortex flows and of the transitional regimes up to the onset of a fully turbulent state. Under these hypotheses, the pressure field is slightly affected by the viscosity variation while dissipative effects are enhanced. The code has been validated by means of comparison with available experimental data. Particular attention is devoted to static working parameters (i.e., equilibrium position and frictional power loss), reproducing the global behavior of the bearing, although some local characteristic is also considered
Methodology for the Residual Axial Thrust Evaluation in Multistage Centrifugal Pumps
One of the most challenging aspects in horizontal pumps design is the evaluation of the residual axial thrust acting on the rotating shaft. The thrust is affected by pump characteristics and working conditions. Solving this problem is easier for a single stage pump than for multistage pumps, even in partially self-balancing opposite impeller configuration. The challenge is then to individuate a procedure that will provide the residual thrust value with a moderate computational effort, dealing with the industrial requests of accuracy and reduced time consumption. A procedure is proposed, which consists in the numerical simulation of each pump component. For each component, the obtained mass-flow/thrust correlations are coupled by using a momentum balance equation used to calculate the axial thrust as a function of the working conditions. The main topic in multistage pump modeling is the leakage flows characterization by means of accurate numerical analysis. Therefore, the cavity flows behavior is investigated and the flow structures individuated. The numerical investigation of the pump’s components provides also a thorough knowledge of fluid dynamic fields. The proposed procedure is able to predict both the direction and the variation of the thrust in a selected range of flow rates, while the value of the thrust is affected by a non-negligible error generated by “real machine” effects
On the Effect of an Aggressive Inlet Swirl Profile on the Aero-thermal Performance of a Cooled Vane
AbstractA high-pressure vane equipped with a realistic film-cooling configuration has been studied. The vane is characterized by the presence of multiple rows of fan-shaped holes along pressure and suction side while the leading edge is protected by a showerhead system. Steady three-dimensional Reynolds-Averaged Navier-Stokes (RANS) simulations have been performed. A preliminary grid sensitivity analysis has been performed (with uniform inlet flow) to quantify the effect of the spatial resolution. Turbulence model has been assessed in comparison with available experiment data. The effects of a realistic inlet swirl on the aero-thermal performance of the cooling system are then investigated by means of comparison between two different kinds of simulations. The first one using a uniform inlet flow while the second one with aggressive swirl derived from the EU-funded project TATEF2. Clocking effects are also accounted for. The effect of the swirling flow in determining the coolant transport are investigated, evidencing the key role that these phenomena have in determining the effectiveness of the cooling
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
On the Assessment of an Unstructured Finite-Volume DES/LES Solver for Turbomachinery Applications
Improvements in mean flow and performances simulation in turbomachinery has brought research to focus more demanding topics like turbulence effects on turbines. Although overall performances are well predicted by Unsteady-RANS, other phenomena such as aerodynamic noise or transition need more accurate prediction of turbulent flow features. Thus different kinds of equation modeling other than URANS are needed to cope with this issue. The success of Detached-Eddy Simulation and Large-Eddy Simulation applications in reproducing physical behavior of flow turbulence is well documented in literature. Despite that, LES simulations are still computationally very expensive and their use for investigating industrial configurations requires a careful assessment of both numerical and closure modeling techniques. Moreover LES solvers are usually developed on a structured mesh topology for sake of simplicity of high-order schemes implementation. Application to complex geometries like those of turbomachinery is therefore difficult. The present work addresses this issue considering the feasibility of converting an operative in-house URANS solver, widely validated for applicative purposes, into higher resolution DES and LES, in order to face turbulence computation of turbomachinery technical cases. The solver presents a 3D unstructured finite-volume formulation, which is kept in LES approach in order to handle complex geometries and it is developed to perform unsteady simulations on turbine stages. Preliminary assessment of the solver has been performed to evaluate and improve the accuracy of the convective fluxes discretization on an inviscid bump test case. First a DES-based approach has been implemented, as it is less computationally challenging and numerically demanding than LES. A square cylinder test case has been assessed and compared with experiments. Then, a pure LES with a Smagorinsky sub-grid scale model has been evaluated on the test case of incompressible periodic channel flow in order to assess the capability of the solver to correctly sustain a time developing turbulent field
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Turbulence and Transition Modeling in Transonic Turbine Stages
This paper describes an in-house approach to the transition evaluation which is compared to conventional turbulence closures in test cases where steady and unsteady heat transfer evaluation is considered. The in-house URANS CFD code HybFlow has been used. The standard k-ω model by Wilcox, the SST model by Menter, the ν’2-f model, the k-ε-kl model of Walters and Leylek and the two equations models coupled with the transport of the intermittency function have been tested. The rationale of the work is to verify the accuracy of turbulence and transition models for heat transfer evaluation and by-pass transition when challenging applicative test cases are considered. The present work was carried out in the frame of the EU funded TATEF2 project
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