1,721,044 research outputs found
Design Strategies and Different Materials for High Efficiency Induction Motors. A Comparison
No full textThe paper presents the results of a research project concerning the efficiency improvement in in-dustrial three-phase induction motors, making use of three different design strategies: substitution of copper cage for aluminium cage with standard and “premium” electrical steel; design optimisa-tion of copper cage motor by changing the stator winding and the stack length only; design optimi-sation of copper cage motor by changing the stator winding, the stack length and the stator and rotor slot shapes. The aim of the project was the analysis and the construction of several prototypes of induction motors by using the above mentioned innovative technological solutions, in order: to compare the design strategies; to verify the actual efficiency improvements, the arrangement of the motors with respect to the European Classification Scheme (EC/CEMEP), the contribution of each material and innovative technology to the efficiency improvements. The paper presents the results related to above mentioned design strategies, and concerns a typi-cal 3 kW, 4 pole, 50 Hz, 400 V, TEFC induction motor. The experimental results presented in the paper refer to the Standard CSA C390-98
SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE.
Full text linkSphingolipids (SLs) are minor cell membrane amphyphilic components, residing in the external layer of the plasma membrane (PM), with the hydrophobic moiety, the ceramide (Cer), inserted into the membrane layer and the hydrophilic head group protruding toward the extracellular environment. They are a family of several compounds with different structural properties: the phospholipid, sphingomyelin (SM), the glycosphingolipids (GSLs) characterized for containing a complex oligosaccharide chain as hydrophilic moiety and gangliosides, GSLs containing sialic acid. As membrane components, SLs participate to modulate several cell processes, such as cell growth, differentiation, morphogenesis, cell to matrix interaction and cell to cell communication. From this, it follows that a defect in SL metabolism can obviously lead to a great number of dysfunctions, ranging from neurodegeneration to cancer.
Along my Ph.D. course I considered the different faces of SLs roles: from their involvement in physiology to that in pathology.
i.SPHINGOLIPIDS and HEALT.
SLs cluster to form SL-enriched domains on cellular PM (lipid rafts, caveolae, and glycosynapses) providing a microenvironment within the PM for reciprocal interaction between lipids and proteins. In particular biochemical analyses have demonstrated that GSLs-enriched microdomains contain several transducer molecules, especially membrane-anchored signal transduction molecules, such as tyrosine kinases belonging to the Src family. Although it has been speculated that GSLs are involved in cell differentiation, proliferation and functions such as phagocytosing, there are quite few evidence that GSLs, by themselves, directly mediate signal transduction, which lead to these cell functions.
LACTOSYLCERAMIDE-ENRICHED MICRODOMAIN in NEUTROPHILIS. Lactosylceramide (LacCer), a neutral GSL, is abundantly expressed on human neutrophils, and specifically recognizes several pathogenic microorganisms. It has been previously demonstrated that LacCer forms PM lipid domains, that can be separated by detergent treatment of cells followed by ultracentrifugation, and that these lipid domains are coupled with Lyn, a Src family kinase. Ligand binding to LacCer activates Lyn, resulting in neutrophils functions, such as superoxide generation, phagocytosis and migration. The presence of LacCer molecular species with Cer containing a very long fatty acid chain is necessary for the association of Lyn with LacCer-enriched PM domains and LacCer-mediated functions. Lyn is associated by a palmitoyl anchor to the cytoplasmic leaflet, while LacCer is inserted into the outer layer of membrane bilayer. So the question is: how does LacCer interact with signal transducer molecules?
The GSL-protein interactions in neutrophilis have been investigated by photoactivable GSLs. These molecules have been administered and taken up by the cell PM. When cells are illuminated, the photoactivable group, linked to the terminal portion of Cer, yields a very reactive intermediate, that covalently binds the molecules in the close environment.
For the first time, at the best of our knowledge, we show a direct connection, across the PM, between GSLs and palmitoylated proteins: these results suggest that LacCer with a long fatty acid chain in Cer moiety could be the key-player of the transduction of information across the PM, modulating membrane interdigitation, through the long acyl chain, and forming specific PM microdomains.
ii. SPHINGOLIPIDS and DISEASES. IMPLICATION IN NEURODEGENERATIVE DISORDERS. SLs are particularly abundant in the nervous system where they play crucial roles regulating signaling events. Severe neurodegeneration is the prominent pathological hallmark of the most sphingolipidoses, inherited metabolic diseases characterized by a defect in the lysosomal GSL catabolism. Most of sphingolipidosis are caused by deficiencies of a specific lysosomal hydrolases, resulting in the accumulation of undegraded lipid metabolite in many cells.
SECONDARY ACCUMULATIONS OF GANGLIOSIDES: THE CASE PF NIEMMAN-PICK TYPE Niemann-Pick Disease (NPD) is a rare, autosomal recessive, lysosomal storage disease resulting from a deficiency in acid sphingomyelinase (ASM) activity. If ASM is absent or not functioning properly, SM cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems. In NPD type A, residual enzyme activity is very low (<5%) and in NPD-A patients, storage pathology is severe within neurons and glial cells throughout the nervous system resulting in progressive, global deterioration of neurological function and death by 3 years of age.
To better understand the secondary biochemical mechanism underling the pathogenesis and the importance of these secondary alterations of SL metabolism on lysosomal diseases, we analyzed lipid composition of CNS and extraneural tissues from the acid sphingomyelinase-deficient (ASMKO) mouse, the animal model of NPD type A, that has been developed using gene targeting and embryo transfer techniques. Our data show an unexpected tissue specific selection of the accumulated molecular species of SM, and an accumulation of GM3 and GM2 gangliosides in both neural and extraneural tissues, that cannot be solely explained by the lack of ASM. In ASMKO mice, we observed the preferential accumulation of SM molecular species with shorter acyl chains in the nervous system, but not in extraneural tissues. The unbalance toward C18/C16-fatty acid containing SM species was detectable as early as SM accumulation started, and monosialoganglioside accumulation followed immediately afterwards. These changes in SL patterns should thus represent the effect of secondary biochemical pathways altered as a consequence of a non-related primary cause. The mechanism underlying these changes still remains to be elucidated and is probably the result of changes in the expression and/or activity of more than one single enzyme, and of anomalies in the traffic of the substrate/product concentrations in multiple cellular compartments. Several pieces of evidence suggest that altered SL metabolism results in a non-physiological PM composition and organization, leading to altered PM-originated signalling pathways that could be relevant to the onset of cellular damage and of tissue pathology.
CHAPERONE THERAPY FOR GM2 GANGLIOSIDOSIS: PYRIMETHAMINE and SANDHOFF DISEASE. Sandhoff disease is an autosomal recessive neurodegenerative disease characterized by the intralysosomal accumulation of GM2 ganglioside. This is due to mutations in the β-hexosaminidases β-chain gene, resulting in a β-hexosaminidases A (αβ) and B (ββ) deficiency. Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER), and most of them are transported to the Golgi apparatus for glycosylation and taggeting for lysosomes, by the addition of mannose-6-phosphate. The ER contains a highly conserved degradation pathway, to protect cells from misfolding and potentially toxic proteins. Thus, the protein turnover ensures integrity and biological functions of cells. Treatment of sphingolipidoses, such as Sandhoff disease, have received increasing interest despite the low incidence. However, the replacing enzyme therapy meets the problem to be ineffective over the blood brain barrier and thus new approaches are now under investigation. One of these is the use of pharmacological chaperones. Pyrimethamine, a drug used to treat or prevent serious parasite infections, such as toxoplasmosis and malaria, has been described to act as chaperone for the β-hexosaminidase. Fibroblasts from two cases of juvenile Sandhoff disease, displaying the new mutations C1082+5G>A (#1) and C446-13A>G (#2) in the HEX B gene, were treated with pyrimethamine. The two examined cell lines, after treatment with pyrimethamine, showed an increased total β-hexosaminidase activity, so that the residual value was around 10%. This value should be enough to limit the accumulation of GM2. In contrast to this, cells treated with pyrimethamine and fed with isotopically tritium labeled ganglioside GM1 did not show any GM2 lysosomal catabolism. This negative result was explained after fractionation of the total cell proteins by ion exchange DEAE column chromatography. Clearly, we found that the increased β-hexosaminidase activity on the artificial substrate was due to the increase of the activity of β-hexosaminidase isoform S. Unlikely, the isoform S, even if it hydrolyzes the artificial compound, does not recognize the natural substrate GM2 and, therefore, the pyrimethamine is unable to modify cell lysosomal activity in the two cell lines showing the new mutations C1082+5G>A and C446-13A>G, and, moreover, cannot be used as a therapeutic drug for the these two patients. Our results are in agreement with a previous information on the selective activity of pyrimethamine depending on the mutation and confirm the advantages deriving from the use of patients’ fibroblasts for the decision on the use of pyrimethamine as therapeutic drug.
IMPLICATION IN CANCER Tumor cells are characterized by aberrant glycosylation processes responsible to increase proliferation and motility. A precise content and molar ratio between SLs is necessary in cells to have the correct membrane organization and the correct interaction processes between membrane components and membranes of adjacent cells.
CELL SURFACE MODULATION DURING TUMOR IRRADIATIONS. Radiotherapy has actually been used clinically for a number of years, with very positive results on tumor reduction. Irradiation of cancer cells leads to cell death by different mechanism. DNA damage, mitochondrial damage and oxidative stress bring mainly to necrosis, whereas the PM production of ceramide leads to apoptosis. The ceramide mediated apoptosis has been reported to depend on activation of cell surface sphingomyelinase and the following activation of the ceramide dependent phosphorylation cascade. Other enzymes of the SL metabolism have been recently found associated to the external leaflet of the PMs, like the α-sialidase, the β-hexosaminidase, the β-galactosidase and the β-glucosidase. These glycohydrolases lead to ceramide from complex GSLs and suggest a new way to trigger the ceramide-induced apoptosis. The PM enzymatic activities display optimal pH under mild acidic condition. This is found in specific membrane domains, known as lipid rafts, where GSLs are highly enriched together with ion exchanger proteins such as proton pumps.
Human breast cancer cell line T47D was studied in detail. In these cells the increase of activity of β-glucosidase and β-galactosidase was parallel to the increase of irradiation dose up to 60 Gy and continued with time, at least up to 72 hr from irradiation. β-glucosidase increased up to 17 times and β-galactosidase up to 40 times with respect to control. Sialidase Neu3 and sphingomyelinase increased about 2 times at a dose of 20 Gy but no further significant differences were observed with increase of radiation dose and time. After irradiation, we observed a reduction of cell proliferation, an increase of apoptotic cell death and an increase of PM ceramide up to 3 times, with respect to control cells. Tritiated GM3 ganglioside has been administered to T47D cells under conditions that prevented the lysosomal catabolism. GM3 became component of the PMs and was transformed into LacCer, GlcCer and ceramide. The quantity of ceramide produced in irradiated cells was about two times that of control cells.
We are characterizing the role of PM glycohydrolases in the process of apoptosis activated by cell irradiation and developing new protocols for radiation therapy combined with pharmacological treatments capable to exert enhanced antitumor activity through synergic action. Increase of the activities of the PM glycohydrolases, and of the apoptotic process, cold be obtained by i) activating with specific drugs the PM proton pumps to decrease the local extracellular pH; ii) the use of recombinant glycohydrolases; iii) using drugs or chaperones capable to modulate directly the glycohydrolase activities. Concerning this last opportunity, molecules acting as chaperones able to up-regulate the activity of lysosomal enzymes are known. Also if no information is available, considering the nature of PM enzymes, we believe that these regulators should be effective also on PM enzymes
La progettazione ottimizzata di trasformatori a secco
No full textViene presentata una procedura di calcolo automatica orientata all’ottimizzazione del progetto di trasformatori in resina di potenza compresa tra 100 e 1000 (kVA).
La procedura e’ abbastanza versatile e consente di scegliere a piacimento la “funzione obiettivo” come anche le variabili indipendenti ed i vincoli sia di natura geometrica che di prestazione.
L’impiego di tale metodologia ha permesso di individuare dei progetti alternativi ottimizzati sia con riferimento al “costo di costruzione” della macchina sia al “costo delle perdite” capitalizzato all'anno di acquisto.
Negli esempi proposti vengono poste a confronto le prestazioni dei nuovi progetti con quelle di trasformatori in resina attualmente in produzione e fornite da un qualificato Costruttore nazionale
Ottimizzazione del Costo di Costruzione di un Motore Asincrono Trifase B.T.: Analisi Economica
No full textNew Materials and Innovative Technologies to Improve the Efficiency of Three-phase Induction Motors. A Case Study
No full textThe paper presents the results of a research project whose aim was the investigation of the efficiency improvement of industrial three-phase induction motors when high quality electrical steel is adopted in combination with die cast copper rotor cage, in order to define the design strategies; to verify the actual efficiency improvements; to verify the arrangement of the motors respect to the European Classification Scheme (EC-CEMEP). The results are related to the cheapest design strategies when “premium steel” and copper rotor cage are used instead of standard steel and aluminum cage, with standard and higher stack length. The considered motor sizes are 3 and 7.5 kW, 4 pole, 50 Hz, 400 V, TEFC
Design Solutions to Optimize Torque Ripple in Synchronous Reluctance Motor
No full textThe paper deals with the minimization of torque ripple in Synchronous Reluctance Motors. It presents the analysis
for the torque prediction pointing out the differential
inductances terms that heavily affects torque profile.
The Finite Element Analysis (FEA) has been used to
evaluate the inductances behavior with rotor position.
The torque ripple has been reduced first with a rotor
skewing, then with a rotor design optimization
Progetto ottimizzato di un Magnete Multipolare per Tomografia a Basso Campo Magnetico
No full textPresso l'Universita' dell'Aquila e' stata realizzata un'apparecchiatura per "imaging" basato sulle risonanze di spin elettronico (EPRI) e sulle doppie risonanze elettroniche-nucleari (PEDRI). Tale apparecchiatura permette di ottenere, a valori di campo magnetico molto inferiori di quello usato per l'imaging diagnostico tramite Risonanze Nucleari, una eguale sensibilita' ed una maggiore specificita'. Essa e' costituita da un magnete multipolare realizzato con lamierini magnetici ad alta permeabilita'.
Il ricorso al Metodo agli Elemeti Finiti ha permesso di ottimizzare il progetto del magnete in modo da garantire una densita' di flusso massima, nella parte centrale, di 0.08 T ed una uniformita' di campo di circa 40 ppm, in una regione sferica di 14 cm
LXR-silencing induces apoptosis by glycosphingolipderived ceramide in different tumor cell type
No full textCell surface ceramide is a key signaling molecule necessary to regulate important cellular processes, like differentiation, proliferation and apoptosis. Its production derives from several sphingolipids, including gangliosides by activity of the plasma membrane glycosidases, like sialidase NEU3, β-HEX, βGAL and β-GLU. We found that several human cancer cell lines (i.e. multiple-myeloma, melanoma and breast cancer) shared the same sensitivity to LXRα signaling abrogation. We focused our attention on one of LXRα target genes, SREBP-1c, a transcription factor regulating de novo lipogenesis, which is the main pathway used by cancer cells for the synthesis of new structural lipids. Both SREBP-1c and its target gene FASN turned out to be down regulated in shLXRα-sensitive but not in shLXRα-insensitive cells. Finally, we have found in the shLXRα-sensitive cells an increase of apoptotic cell death due to an increase of PM ceramide up to 3 times with respect to the shLXRα-insensitive cells. We also observe a reduction in ganglioside GM3, suggesting that ceramide is because of the activity of PM sialidase NEU3, β-GAL and β-GLU. These data suggest that in shLXRα-sensitive cells the tumor-promoting role of LXRα might be due to an effect on the SREBP-1c-driven de novo lipogenesis. FASN inactivation could be responsable for a reorganization of cell membrane given a decrease in the synthesis of FA, therefore an alteration of lipid metabolism: increase in glycohydrolase activity and in PM GM3, LacCer, GlcCer and pro-apoptotic ceramide. This pathway may represent a novel potential drug-target in multiple-myeloma and other tumors
- …
