484 research outputs found

    Energy Analysis of UC3M Campus of Leganes and Colmenarejo: Introducing photovoltaic generation

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    Spanish’s energy market is experiencing big changes. Renewable energy sources and decentralization of production are on the rise. An example of this is PV systems for self- consumption with or without batteries, in houses or other buildings. One clear advantage of this is the reduction of transmission losses. In addition, this type of systems will serve to reduce CO2 emissions and allow for a better implementation of electric cars in today’s society. The aim of this thesis is to analyse the solar potential of the UC3M Campus of Leganés and Campus of Colmenarejo. Installed capacity in both campus will be maximised in an attempt to achieve “full self-consumption”, defined as the point where yearly energy generated and consumption level off. System Advisor Model will be used to simulate PV generation. This term is ambiguous, as it seems that it refers to independence from the grid and 100% renewable penetration. However, it is a reflection of the PV potential of the location at hand. Spanish regulatory framework regarding the energy sector has been modified twice in the last year. The recent Royal Decree (RD 244/2019) will be explained, allowing for a better understanding of each scenario studied. Moreover, a statistical analysis of the demand and generation for both campuses will be performed, using various tools. A Matlab script has been created for this task and to store all data found, which may serve for future work regarding the university. Results showed that over 1MW of capacity was installed in Leganés, and around 10MW in Colmenarejo, which had land available for the panels. From this project, it was concluded that full self-consumption is feasible in Colmenarejo (827.63MWh) but not in Leganés (7.85GWh), as demand is larger and space limited. For a combined case, using space from both campuses to meet their total demand, full self- consumption is achieved (8.68GWh). In addition, if remuneration of excess energy (see section [1.1.2.2]) was aimed, only Colmenarejo would be an option, with a total of 11.3 MWh a year of injected energy. A 100kW system would produce no excess energy with Leganés’ consumption. This means that for every scenario but the first one mentioned, all energy injected to the grid would mean losses, with the current regulatory framework. Moreover, the use of batteries with total power capacity of 500kW in Leganés would be beneficial from an energy point of view, allowing for a reduction in injected energy of around 37MWh in the first year. For the combination of both cases, with a total power capacity of 3MWh, injections would be reduced to 1GWh annually.Ingeniería de la Energí

    Lipids and Membrane Lateral Organization

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    Shortly after the elucidation of the very basic structure and properties of cellular membranes, it became evident that cellular membranes are highly organized structures with multiple and multi-dimensional levels of order. Very early observations suggested that the lipid components of biological membranes might be active players in the creation of these levels of order. In the late 1980s, several different and diverse experimental pieces of evidence coalesced together giving rise to the lipid raft hypothesis. Lipid rafts became enormously (and, in the opinion of these authors, sometimes acritically) popular, surprisingly not just within the lipidologist community (who is supposed to be naturally sensitive to the fascination of lipid rafts). Today, a PubMed search using the key word “lipid rafts” returned a list of 3767 papers, including 690 reviews (as a term of comparison, searching over the same time span for a very hot lipid-related key word, “ceramide” returned 6187 hits with 799 reviews), and a tremendous number of different cellular functions have been described as “lipid raft-dependent.” However, a clear consensus definition of lipid raft has been proposed only in recent times, and the basic properties, the ruling forces, and even the existence of lipid rafts in living cells has been recently matter of intense debate. The scenario that is gradually emerging from the controversies elicited by the lipid raft hypothesis emphasizes multiple roles for membrane lipids in determining membrane order, that encompass their tendency to phase separation but are clearly not limited to this. In this review, we would like to re-focus the attention of the readers on the importance of lipids in organizing the fine structure of cellular membranes

    Sphingolipids and neuronal degeneration in lysosomal storage disorders

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    Ceramide, sphingomyelin, and glycosphingolipids (both neutral and acidic) are characterized by the presence in the lipid moiety of an aliphatic base known as sphingosine. Altogether, they are called sphingolipids and are particularly abundant in neuronal plasma membranes, where, via interactions with the other membrane lipids and membrane proteins, they play a specific role in modulating the cell signaling processes. The metabolic pathways determining the plasma membrane sphingolipid composition are thus the key point for functional changes of the cell properties. Unnatural changes of the neuronal properties are observed in sphingolipidoses, lysosomal storage diseases occurring when a lysosomal sphingolipid hydrolase is not working, leading to the accumulation of the substrate and to its distribution to all the cell membranes interacting with lysosomes. Moreover, secondary accumulation of sphingolipids is a common trait of other lysosomal storage diseases

    Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases

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    The central nervous system is characterized by a high content of sphingolipids and by a high diversity in terms of different structures. Stage- and cell-specific sphingolipid metabolism and expression are crucial for brain development and maintenance toward adult age. On the other hand, deep dysregulation of sphingolipid metabolism, leading to altered sphingolipid pattern, is associated with the majority of neurological and neurodegenerative diseases, even those totally lacking a common etiological background. Thus, sphingolipid metabolism has always been regarded as a promising pharmacological target for the treatment of brain disorders. However, any therapeutic hypothesis applied to complex amphipathic sphingolipids, components of cellular membranes, has so far failed probably because of the high regional complexity and specificity of the different biological roles of these structures. Simpler sphingosine-based lipids, including ceramide and sphingosine 1-phosphate, are important regulators of brain homeostasis, and, thanks to the relative simplicity of their metabolic network, they seem a feasible druggable target for the treatment of brain diseases. The enzymes involved in the control of the levels of bioactive sphingoids, as well as the receptors engaged by these molecules, have increasingly allured pharmacologists and clinicians, and eventually fingolimod, a functional antagonist of sphingosine 1-phosphate receptors with immunomodulatory properties, was approved for the therapy of relapsing-remitting multiple sclerosis. Considering the importance of neuroinflammation in many other brain diseases, we would expect an extension of the use of such analogs for the treatment of other ailments in the future. Nevertheless, many aspects other than neuroinflammation are regulated by bioactive sphingoids in healthy brain and dysregulated in brain disease. In this review, we are addressing the multifaceted possibility to address the metabolism and biology of bioactive sphingosine 1-phosphate as novel targets for the development of therapeutic paradigms and the discovery of new drugs

    Gangliosides as components of lipid membrane domains

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    Cell membrane components are organized as specialized domains involved in membrane-associated events such as cell signaling, cell adhesion and protein sorting. These membrane domains are enriched in sphingolipids and cholesterol, but display a low protein content. Theoretical considerations and experimental data suggest that some properties of gangliosides play an important role in the formation and stabilization of specific cell lipid membrane domains. Gangliosides are glycolipids with strong amphiphilic character and are particularly abundant in the plasma membranes, where they are inserted into the external leaflet with the hydrophobic ceramide moiety and with the oligosaccharide chain protruding into the extracellular medium. The geometry of the monomer inserted into the membrane, largely determined by the very large surface area occupied by the oligosaccharide chain, the ability of the ceramide amide linkage to form a network of hydrogen bonds at the water-lipid interface of cell membranes, the Delta(4) double bond of sphingosine proximal to the water-lipid interface, the capability of the oligosaccharide chain to interact with water, and the absence of double bonds into the double-tailed hydrophobic moiety, are the ganglioside features that will be discussed in this review, to show how gangliosides are responsible for the formation of cell lipid membrane domains characterized by strong positive curvature

    Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

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    Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets

    Human Remyelination Promoting Antibody Stimulates Astrocytes Proliferation Through Modulation of the Sphingolipid Rheostat in Primary Rat Mixed Glial Cultures

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    Remyelination promoting human IgMs effectively increase the number of myelinated axons in animal models of multiple sclerosis. Hence, they ultimately stimulate myelin production by oligodendrocytes (OLs); however, their exact mechanism of action remains to be elucidated, and in particular, it remains unclear whether they are directly targeting OLs, or their action is mediated by effects on other cell types. We assessed the effect of remyelination promoting antibody rHIgM22 on the proliferative response and on the ceramide/sphingosine 1-phosphate rheostat in mixed glial cell cultures (MGCs). rHIgM22 treatment caused a time-dependent increase in PDGF\u3b1R protein in MGCs. Forty-eight hours of treatment with rHIgM22 induced a dose-dependent proliferative response (evaluated as total cell number and as EdU(+) cell number) in MGCs. When the proliferation response of MGCs to rHIgM22 was analyzed as a function of the cell types, the most significant proliferative response was associated with GLAST(+) cells, i.e., astrocytes. In many cell types, the balance between different sphingolipid mediators (the "sphingolipid rheostat"), in particular ceramide and sphingosine 1-phosphate, is critical in determining the cell fate. rHIgM22 treatment in MGCs induced a moderate but significant inhibition of total acidic sphingomyelinase activity (measured in vitro on cell lysates), the main enzyme responsible for the stimulus-mediated production of ceramide, when treatment was performed in serum containing medium, but no significant differences were observed when antibody treatment was performed in the absence of serum. Moreover, rHIgM22 treatment, either in the presence or in absence of serum, had no effects on ceramide levels. On the other hand, rHIgM22 treatment for 24\ua0h induced increased production and release of sphingosine 1-phosphate in the extracellular milieu of MGC. Release of sphingosine 1-phosphate upon rHIgM22 treatment was strongly reduced by a selective inhibitor of PDGF\u3b1R. Increased sphingosine 1-phosphate production does not seem to be mediated by regulation of the biosynthetic enzymes, sphingosine kinase 1 and 2, since protein levels of these enzymes and phosphorylation of sphingosine kinase 1 were unchanged upon rHIgM22 treatment. Instead, we observed a significant reduction in the levels of sphingosine 1-phosphate lyase 1, one of the key catabolic enzymes. Remarkably, rHIgM22 treatment under the same experimental conditions did not induce changes in the production and/or release of sphingosine 1-phosphate in pure astrocyte cultures. Taken together, these data suggest that rHIgM22 indirectly influences the proliferation of astrocytes in MGCs, by affecting the ceramide/sphingosine 1-phosphate balance. The specific cell population directly targeted by rHIgM22 remains to be identified, however our study unveils another aspect of the complexity of rHIgM22-induced remyelinating effect

    Altered expression of ganglioside GM3 molecular species and a potential regulatory role during myoblast differentiation

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    Gangliosides (sialic acid-containing glycosphingolipids) help regulate many important biological processes, including cell proliferation, signal transduction, and differentiation, via formation of functional microdomains in plasma membranes. The structural diversity of gangliosides arises from both the ceramide moiety and glycan portion. Recently, differing molecular species of a given ganglioside are suggested to have distinct biological properties and regulate specific and distinct biological events. Elucidation of the function of each molecular species is important and will provide new insights into ganglioside biology. Gangliosides are also suggested to be involved in skeletal muscle differentiation; however, the differential roles of ganglioside molecular species remain unclear. Here we describe striking changes in quantity and quality of gangliosides (particularly GM3)during differentiation of mouse C2C12 myoblast cells and key roles played by distinct GM3 molecular species at each step of the process
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