2,611 research outputs found

    LPIAT1/MBOAT7 contains a catalytic dyad transferring polyunsaturated fatty acids to lysophosphatidylinositol.

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    Abstract Human membrane bound O-acyltransferase domain-containing 7 (MBOAT7), also known as lysophosphatidylinositol acyltransferase 1 (LPIAT1), is an enzyme involved in the acyl-chain remodeling of phospholipids via the Lands' cycle. The MBOAT7 rs641738 variant has been associated with the entire spectrum of fatty liver disease (FLD) and neurodevelopmental disorders, but the exact enzymatic activity and the catalytic site of the protein are still unestablished. Human wild type MBOAT7 and three MBOAT7 mutants missing in the putative catalytic residues (N321A, H356A, N321A + H356A) were produced into Pichia pastoris, and purified using Ni-affinity chromatography. The enzymatic activity of MBOAT7 wild type and mutants was assessed measuring the incorporation of radiolabeled fatty acids into lipid acceptors. MBOAT7 preferentially transferred 20:4 and 20:5 polyunsaturated fatty acids (PUFAs) to lysophosphatidylinositol (LPI). On the contrary, MBOAT7 showed weak enzymatic activity for transferring saturated and unsaturated fatty acids, regardless the lipid substrate. Missense mutations in the putative catalytic residues (N321A, H356A, N321A + H356A) result in a loss of O-acyltransferase activity. Thus, MBOAT7 catalyzes the transfer of PUFAs to lipid acceptors. MBOAT7 shows the highest affinity for LPI, and missense mutations at the MBOAT7 putative catalytic dyad inhibit the O-acyltransferase activity of the protein. Our findings support the hypothesis that the association between the MBOAT7 rs641738 variant and the increased risk of NAFLD is mediated by changes in the hepatic phosphatidylinositol acyl-chain remodeling. Taken together, the increased knowledge of the enzymatic activity of MBOAT7 gives insights into the understanding on the basis of FLD

    Il motore elettrico: un integratore perfetto?

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    Viene preso in esame l'uso del motore in corrente continua come servomotore e viene presentato un metodo per approssimarne il comportamento a quello di un motore ideale

    The History of Photovoltaics with Emphasis on CdTe Solar Cells and Modules

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    Among thin-film photovoltaic technology, cadmium telluride (CdTe) has achieved a truly impressive development that can commercially compete with silicon, which is still the king of the market. Solar cells made on a laboratory scale have reached efficiencies close to 22%, while modules made with fully automated in-line machines show efficiencies above 18%. This success represents the result of over 40 years of research, which led to effective and consolidated production processes. Based on a large literature survey on photovoltaics and on the results of research developed in our laboratories, we present the fabrication processes of both CdTe polycrystalline thin-film solar cells and photovoltaic modules. The most common substrates, the constituent layers, their interaction, the interfaces and the different “tricks” necessary to obtain highly efficient devices will be analyzed. A realistic industrial production process will be analytically described. Moreover, environmental aspects, end-of-life recycling and the life cycle assessment of CdTe-based modules will be deepened and discussed

    Beam loading assisted matching working point for PWFA beam driven experiment at SPARC_LAB

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    This thesis concerns the investigation of the methods to improve the quality of beams accelerated via beam-driven plasma wakefield acceleration (PWFA) schemes in therms of emittance and energy spread. In the I chapter the motivation that led to the use of plasma wakefields in order to accelerate beams instead of conventional RF-based accelerating structures is reviewed, reporting also the state of the art of beam driven PWFA experiments. Investigating the differences between linear and non linear plasma wake, a proposal for a new scheme is elaborated. This scheme is based on the combination of a low quality high charge driver that generates an accelerating wakefield in linear regime and an high quality low charge witness that is injected in a region close to the crest of the accelerating wakefield. Since most of the focusing field is guaranteed by the beam loading effect, this scheme was called Beam Loading ASsisted maTching (BLAST) scheme. The theoretical tools to develope the study of this kind of working point are also discussed. The II chapter introduces the models used to describe the fields inside plasma. The very well-estabilished plasma linear theory will be developed in electrostatic approximation in order to derive a complete solution of the fields in the entire space. This solution will be used to obtain scaling laws that describe the main features of plasma acceleration i.e. maximum attainable energy, expected energy spread growth and optimal injection phase of witness for beam loading compensation of energy spread. The solution for the transverse field will be used in order to find the matching conditions via the envelope equation. Finally a procedure for the design of BLAST working points will be presented. The III chapter will introduce the SPARC\_LAB facility, pointing out the features of the injector and the experimental setup for the plasma acceleration experiments. In chapter IV the scaling laws derived in chapter II will be verified through the simulation of a working point for an experiment of high quality plasma acceleration to be performed at SPARC\_LAB. The robustness of this working point will be also investigated through a tolerance analysis

    The PNPLA3 I148M variant and chronic liver disease : When a genetic mutation meets nutrients

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    Abstract The isoleucine to methionine substitution at position 148 in the patatin-like phospholipase domain containing 3 protein (PNPLA3; I148M variant, rs738409) is associated with liver fat accumulation and an increased risk of chronic liver disease ranging from hepatitis to hepatocellular carcinoma. This review discusses the interaction between the PNPLA3 I148M variant and obesity/intake of specific nutrients in determining the susceptibility to liver disease. We present the results of several studies showing that obesity or alcohol abuse enhances the effect of the PNPLA3 I148M variant on the liver. We also show that specific nutrients interact with the PNPLA3 I148M variant in modulating liver disease susceptibility

    Innervation of a prefabricated flap: a new experimental model.

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    Introduction. Flap innervation by neoaxonogenesis is a promising field of investigation. The authors evaluated the possibility of innervating an acellular collagen scaffold as component of a potential prefabricated flap. Materials and Methods. Collagen matrix sheets were implanted around the femoral bundle of a murine model to produce two flaps on proximal and distal nerve stumps based on a flow-through model. After thirty days, nerve regeneration and integration into the collagen matrix were evaluated. The specimens were microscopically analyzed to study Schwann cell colonization and axonal integration with the matrix. Axonal count and density were assessed and statistically evaluated. Results. Qualitative structural and ultrastructural evaluation indicated integration, with axonal fibers merged within the collagen matrix, along with a newly formed vascular network on the proximal flap. Wallerian degeneration occurred inside the distal chamber. Axonal count and density did not show statistically significant differences between the nerve inside the proximal flap and the control side. Conclusions. Innervation of an acellular matrix can be obtained by direct nerve stump implantation. The flow-through system was relatively easy to build and reliable to provide adequate blood supply. The collagen scaffold may be a promising support or further studies of preinnervated microsurgical flaps
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