1,355,382 research outputs found
Computational Study Of Diffuser Augmented Wind Turbine Using Actuator Disc Force Method
No full textIn this paper, a computational approach, based on the solution of Reynolds-averaged-Navier–Stokes (RANS) equations, to describe the flow within and around a diffuser augmented wind turbine (DAWT) is reported. In order to reduce the computational cost, the turbine is modeled as an actuator disc (AD) that imposes a resistance to the passage of the flow. The effect of the AD is modeled applying two body forces, upstream and downstream of the AD, such that they impose a desired pressure jump. Comparison with experiments carried out in similar conditions shows a good agreement suggesting that the adopted methodology is able to carefully reproduce real flow features
Multi-element ducts for ducted wind turbines: A numerical study
No full textMulti-element ducts are used to improve the aerodynamic performance of ducted wind turbines (DWTs). Steady-state, two-dimensional computational fluid dynamics (CFD) simulations are performed for a multi-element duct geometry consisting of a duct and a flap; the goal is to evaluate the effects on the aerodynamic performance of the radial gap length and the deflection angle of the flap. Solutions from inviscid and viscous flow calculations are compared. It is found that increasing the radial gap length results in an augmentation of the total thrust generated by the DWT, whereas a larger deflection angle has an opposite effect. Reasonable to good agreement is seen between the inviscid and viscous flow calculations, except for multi-element duct configurations characterized by large flap deflection angles. The viscous effects become stronger at large flap deflection angles, and the inviscid calculations are incapable of taking this phenomenon into account.</p
Analisi sperimentale sull’erosione prodotta a valle di grandi dighe
No full textL’erosione a valle di grandi dighe è dovuta all’impatto dei getti ad alta velocità uscenti dagli organi di sfioro delle strutture di ritenuta. Ai fini della scelta del dispositivo di dissipazione è opportuno stimare già in fase di progettazione preliminare la geometria dello scavo e la sua configurazione di equilibrio, in modo da evitare lo scalzamento delle fondazioni della diga e la destabilizzazione dei versanti. Gli AA. riferiscono sui risultati sperimentali, condotti su un modello in similitudine di Froude, per cinque diverse condizioni di esercizio, sull’erosione prodotta al piede di una diga con dissipatore a salto di sci; viene inoltre discussa l’applicabilità delle formule empiriche presenti in letteratura e i risultati comparati in termini di profondità di scavo di equilibrio.Scour downstream of large dams is due to high-velocity jet impact issuing from water releasing structures. The geometry of the hole and the equilibrium scour depth should be carefully estimated in the design phase to prevent undermining of the dam's foundation or side slopes during the operation lifetime. The paper presents an analysis of a dam plunge pool, making use of laboratory observations on a small-scale model in Froude similitude, under different flow conditions, to perform a comparative analysis between scour estimation methods. The application of empirical formulas specifically to ski-jump jets is discussed and results are compared in terms of ultimate scour depth
Addomesticamento delle acque e costruzione delle dighe in Puglia
No full textIl saggio tratta della costruzione delle dighe in Puglia, a partire dagli anni Trenta del Novecento, come strumento di politica economica, volto a risolvere il problema dell'arretratezza delle regioni meridionali. Il progetto non produsse sviluppo e forzò il naturale equilibrio tra popolazioni e territorio
Unraveling the Mechanism of Luteinizing Hormone Receptor Activation : Hinge Region as a Key Player
No full textGPCRs, influencing myriads of cellular functions, are the members of the largest family of the membrane proteins. However, their structures and the signaling mechanisms still remain enigmatic. In case of the Glycoprotein Hormone Receptor (GpHR) family the structure-function relationship is less understood because of a large extra-cellular domain (ECD). This large ECD, consisting of Leucine Rich Repeats (LRRs) and membrane-proximal hinge region, is sufficient for specific binding to the hormone (Ascoli, Fanelli, & Segaloff, 2002), but for receptor activation, hormone binding is translated via a conformation wave starting at hinge region and relayed to the transmembrane domain. Several biochemical, immunological and molecular biological tools have been employed to elucidate the structure-function relationship of the hormones and their receptors. These studies also helped in deciphering some of the regions present in both the hormones and the receptors involved in maintaining the specificity of their interaction (Fan & Hendrickson, 2005; Fox, Dias, & Van Roey, 2001; Wu, Lustbader, Liu, Canfield, & Hendrickson, 1994). However, the complete understanding of the hormone‐receptor contact sites and mechanism of receptor activation are still an enigma. Understanding the molecular details of these phenomena can lead to the development of novel strategies of regulating hormone action or regulating receptor activation in a hormone independent manner.
The crystal structure of FSHR ECD (amino acids 17-366) revealed that LRRs form a semicircular palm shaped structure with the C terminus region, designated as the hinge region, protruding out like a thumb. The hinge region, rather than being a separate functional unit, was found to be an integral part of the LRR domain, having two such repeats (LRR11 &12). LRR 11 is connected to LRR12 through a hairpin loop (amino acids 280-344) harboring the invariant sulfated tyrosine residue (sTyr) in YD/EY motif (X. Jiang et al., 2012). The heterodimeric hormones consisting of a common subunit and a hormone specific subunit, bind to the primary hormone binding site at LRR 4-6 as reported in the FSHR-FSH co crystal (Fan & Hendrickson, 2005). This primary binding of the hormone at LRR 4-6 creates a pocket (comprising of the residues P16α, L17α, F18α, F74α, L37β, Y39β, and P45β) in the hormone for secondary binding at sTyr residue. This interaction is proposed to initiate conformation change in the hinge region which further leads to FSHR activation (X. Jiang et al., 2012). Thus, the role of hinge region in GpHR activation got evolved from a linker to a switch, which decides the fate of the receptor activity (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). sTyr residue being conserved, presents itself as a potential player in activation mechanism of all the three receptors of the family (Bonomi, Busnelli, Persani, Vassart, & Costagliola, 2006; Kreuchwig, Kleinau, & Krause, 2013). Precise involvement of sTyr in GpHR activation is yet to be explored. The previous studies from the laboratory using the hinge region specific polyclonal and monoclonal antibodies established the unequivocal role of the hinge region in FSHR and TSHR activation (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). However, its function in LHR activation has not been conclusively established. Due to the unavailability of the structural information of LHR ECD/hinge, it is more difficult to study and explain the role of hinge region in LHR activation. The hormone independent signaling by point mutants of LHR also remains poorly understood.
In the present study an attempt has been made to understand the role of the hinge region in LHR signaling and modulating role of LRRs in hinge mediated LHR activation. The present study was initiated with an overall objective of understanding the molecular details of LHR activation mechanism keeping hinge at the centre of the picture. To have clarity of this picture with a holistic view of the mechanism, multi-pronged approach was adopted. Initially, ScFvs against LHR hinge region were employed as tools to probe into the hormone‐receptor interactions. Antibodies against glycoprotein hormones and their receptors have often provided insights into the mechanism of hormone‐receptor interactions and signal transduction (Agrawal & Dighe, 2009; Dighe & Moudgal, 1983; Gadkari, Sandhya, Sowdhamini, & Dighe, 2007; Gadkari et al., 2007; Kene, Nalavadi, Dighe, Iyer, & Mahale, 2004; Majumdar, Railkar, & Dighe, 2012a, 2012b). In this study, Single chain Fragment variables (ScFvs) against the hinge region of LH receptor have been employed to understand the mechanism of receptor activation. The effects of LHR ScFvs on hCG-LHR interactions have been investigated and three of the ScFvs, JE10, JE4 and JG1 could bypass the hormone and activate the receptor directly, with JE10 being the most potent one. The effect on the signaling was specific for LHR as no increase in cAMP response was observed for TSHR/FSHR in presence of these ScFvs. JE10 surprisingly was unique and could alter the hCG-LHR interaction by decreasing hormone affinity and simultaneously increasing the Bmax for the hormone. JE10 binding was decreased to the pre-formed hormone receptor complex suggesting that hCG and the stimulatory antibody show stearic hindrance at the binding sites on hinge or hormone binding induces conformational change in the epitope of JE10. The change in affinity and Bmax of the hormone by JE10 could be due to unmasking of new binding sites for hormones or an allosteric effect on the protomer interaction like explained
in case of a small TMD specific allosteric modulator of FSHR (Xuliang Jiang et al., 2014). JE10 could also potentiate hCG signaling at sub-saturating concentrations of hCG, the precise mechanism of which is not clear. Through TSHR-LHR chimeric mutants, a stretch from amino acids 313-349, within the hinge region, was identified as the site recognized by JE10.
In order to study structural features of the JE10 epitope, LHR ECD was modeled on the basis of FSHRED crystal structure. With most of the motifs being structurally conserved (CF3 and YPSHCCAFF); the major portion of the hinge region was found to be unstructured. This unstructured region harbored the JE10 epitope as well as the functionally important conserved sTyr residue. The CD spectra of LHR hinge in presence of ScFv JE10 suggested a ScFv induced helical conformation and stabilization of the hinge loop region, which was constrained in the homology model into helices. As loop was now constrained in the Mode 2, so was the interaction of sTyr, which was now in contact with positively charged residues, probably stabilizing its charge. The YEY motif mutants further confirmed the indirect essential role of Y331 in activation of LHR by JE10.
Another approach followed to study hCG-LHR interactions was use of a series of LHR N-terminal truncation mutants and truncation mutants along with one of the LHR CAM (S277Q/D578Y). The effect of these truncations on hormone binding and receptor activation was investigated. The deletion of Cysteine box (Cb-1) of LHR (present at N-terminus of ECD) leads to abrogation of hCG binding, indicating importance of this region in maintaining ECD conformation required for hormone binding. This is the most unexplored region of the ECD. Though Cb-1 does not bind to the hormone directly (as is evident from the crystal structure) but it is indirectly essential for hormone binding. The basal activity of these truncated mutants was as low as that of the wild type LHR, reconfirming that no region of LHR ECD acts as an inverse agonist for the TMD (Karges, Gidenne, Aumas, Kelly, & Milgrom, 2005). Truncation mutants with CAM (double mutants) also showed low basal activity, suggesting that intact ECD is prerequisite for keeping LHR in a conformation, best suited for hormone binding and binding of G protein for activation. That best conformation still needs to be explored. Truncation mutants did not get stimulated by JE10 also. This observation is opposite to the previous studies in which FSHR/TSHR truncated mutants could be stimulated by hinge specific antibodies (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). This difference points out to the variations in which LHR hinge-TMD interactions prevail and lead to the receptor activation. This variation was also
confirmed with a previous report in which the binding of TSHR-ECL specific antisera to wild type LHR and TSHR-LHR 6 chimeric mutant suggested that hinge of LHR does not seem to be constraining the TMD (Majumdar et al., 2012b). Thus the LHR TMD itself possesses all the inhibitory interactions, also indicated by the presence of most of the activating mutations in LHR TMD (Piersma, Verhoef-post, Berns, & Themmen, 2007).
Protomer interaction is the newest aspect of GpHR activation mechanism and has not reached any conclusive, physiologically relevant explanations yet. By co-transfection of wild type LHR and ECD truncated mutants, this study suggests the LHR protomer interaction and proposes the involvement of allosteric effect of ECD on LHR protomer interaction.
The effect of JE10 on activating and inactivating mutants of LHR were quite interesting. The ScFv could bind to the activating mutant D578Y (associated with precocious puberty). This mutant exhibited higher basal cAMP production, but was activated even further by the ScFv. The inactivating mutant A593P is a completely inactive receptor associated with (associated with pseudo-hermaphroditism. It does not respond to the hormone at all. The ScFv JE10 binds to this receptor and stimulates cAMP production. This observation is rather striking, as it is possible to activate a completely inactive mutant that could not be stimulated by the hormone by a binder specific for the hinge region. It is not clear how the binder that interacts with the hinge region affects the function of the inactive TMD thus providing an interesting tool to investigate the interactions between the hinge region and TMD that are probably key to understand the activation of GpHR. which has been shown to be central to the GpHR activation mechanism, (Agrawal & Dighe, 2009; Majumdar et al., 2012b; Schaarschmidt, Huth, Meier, Paschke, & Jaeschke, 2014). As per the recently suggested model by Deupi et. al., that each mutation and agonist can take a different pathway during activation (Kobilka & Deupi, 2007). The activated state induced by JE10 in D578Y and A593P seems to be different from the wild type LHR, with each activated receptor state having different capacity to bind to the G protein. The difference in G protein capacity in itself reflects the different receptor turnover or different Gs uncouplings or different Gs binding affinities, which needs to be further investigated, opening up another avenue for exploration. There is a lacuna in understanding the signal relay from the hinge to TMD. However, JE10 seems to be activating the wild type LHR and the mutants directly or indirectly by modulating the 6th helix of the TMD, known to be important for hormone independent
activation of LHR (Fanelli, 2000; Latronico & Segaloff, 2007; Majumdar et al., 2012b).
As evident from the absence of any hinge mediated constrain on LHR TMD and absence of uncharged residues present in LHR LRRD-TMD interface (LHR ECD Model 1), LHR hinge does not seem to be maintaining significant interactions with the TMD in absence of a ligand or in its basal state. Hormone/ agonist binding or activating mutations act as a positive regulator (inducing conformation change in hinge), required to bridge the interactions between LHR hinge and the TMD, which is supported by various studies in the past (Karges et al., 2005; Majumdar et al., 2012b; Nishi, Nakabayashi, Kobilka, & Hsueh, 2002; Osuga et al., 1997; Ryu, Gilchrist, Tung, Ji, & Ji, 1998; Zeng, Phang, Song, Ji, & Ji, 2001). This interaction bridged by the conformational change in the hinge region, seems to isomerize the closed state of LHR into an activated state. The present study supports the conformational induction model for receptor activation in which intramolecular interactions between the two domains (hinge-TMD) lead to the receptor activation.
In conclusion, this study presents a possible mechanism of activation of LHR by a partial agonist ScFv, which induces the conformation change in the disordered loop region (a.a.313-349) of the hinge and stabilizes it into helical state. This conformation change is predicted to be important for relaying the activation signal to the TMD. The study also demonstrates the activation of a completely inactive mutant A593P by JE10, suggesting a distinct possibility of its use as a therapeutic tool in treating infertility caused by inactivating mutations in LHR.
On a second note, the study extends the role of LRRs, apart from direct hormone binding, to an indirect allosteric role in hormone binding, LHR activation and functional stability. This functional stability does not seem to be restricted to a single LHR but also depends on its interaction with nearby protomers. Though there are evidences for and against each of the above discussed possibilities, as yet there is no accepted model that explains the precise steps of receptor activation, hence, the molecular details of these interactions needs to be investigated in future
Dighe della Sardegna
No full textLa realizzazione di un sistema di dighe e di infrastrutture per la distribuzione idrica ed elettrica nella Sardegna del primo Novecento venne progettata da Angelo Omodeo. Lombardo di nascita l’ingegnere Omodeo (1876-1941) intendeva risolvere alcuni tra i problemi che da sempre affliggevano la Sardegna: la presenza di vaste aree paludose e malarigene, la carenza di acqua, l’assenza di risorse energetiche. A partire dai suoi studi la storia delle bonifiche in Sardegna s’intrecciava con quella delle dighe, possenti strutture chiamate a razionalizzare la raccolta, il deflusso e l’uso delle acque accumulate in grandi invasi artificiali. All’ingegnere si deve la progettazione dei primi grandi sbarramenti — la diga sul Tirso a lungo fu la più grande d’Europa — che, chiamati ad assumere molteplici funzioni, erano realizzati tanto per favorire lo sviluppo dell’economia agraria e industriale, quanto per fare fronte ai bisogni di energia elettrica e di acqua potabile. Le sue tesi furono quindi decisive nell’avviare a soluzione la secolare questione idraulica in Sardegna; si rivelarono, invece, insufficienti a eliminare la malaria – del tutto eradicata dall’isola solo nel secondo dopoguerra –, e a risolvere gli squilibri ambientali, economici e sociali che connotavano il rapporto tra popolazione e territorio, tra campagne, rendita fondiaria e comunità contadine
Dighe e bacini artificiali tra sviluppo economico e questioni ambientali
No full textIl saggio affronta il tema della costruzione di dighe e bacini artificiali in Italia dal primo decollo industriale di fine Ottocento, inizio Novecento, ad oggi. In modo particolare, lo sviluppo dell'industria idroelettrica è messa in relazione con i diversi percorsi di crescita economica dell'Italia nel corso del XX secolo e con le questioni ambientali che esso pone costantemente
Valutazione dell'apporto di sedimenti alle dighe italiane
No full textLAUREA MAGISTRALETanto maggiore è la rilevanza di natura globale del fenomeno dell’interrimento degli invasi artificiali, quanto più necessaria sarà la sua gestione. L’obiettivo di questa tesi è quello di valutare l’apporto solido alle dighe italiane, che fornisce, sebbene attraverso approssimazioni, una misura del fenomeno della sedimentazione nelle dighe italiane. Dall’acquisizione di dati relativi a 50 dighe italiane, è stato possibile ricavare una misura del volume di interrimento, utile per definire la quantità di apporto di sedimenti medio annuo osservato in ingresso alle dighe. I dati raccolti, tuttavia, non erano sufficienti per operare una modellazione dell’apporto solido alle dighe analizzate tramite l’impiego di modelli già esistenti. Tramite l’applicazione quindi, della Revised Universal Soil Loss Equation (modello RUSLE), è stata ricavata una stima della perdita di suolo media annua sull’area dei bacini considerati. Dopo la definizione del dataset di osservazioni di SDR, si è applicata un’analisi di regressione multilineare partendo da un set di 12 variabili esplicative scelte per caratterizzare i bacini esaminati. Più specificamente, l’analisi è stata condotta in parallelo su due differenti campioni di Sediment Delivery Ratio (SDR), uno rappresentativo dei bacini collocati nell’area geografica caratterizzata dalla presenza delle Alpi e l’altro rappresentativo dei bacini collocati nell’area geografica caratterizzata dalla presenza degli Appennini.As the amount of the attention payed to reservoir’s sedimentation increases, the need for its management grows even more. The objective of the thesis is to evaluate the Specific Sediment Yield (SSY) at the Italian dam’s reservoirs which can approximately provide a measure of the reservoir’s sedimentation at the Italian dams. By collecting data from 50 italian dams, it was possible to estimate the measure of the volume of sediments inside the reservoirs. This measure was then used to define the Specific Sediment Yield observed at the dam’s reservoirs. Objectively, the available data were just too few to implement any existing model as well as to compute the estimates for the observed values of SSY. Instead, it was the application of the Revised Universal Soil Loss Equation (RUSLE model) that made possible the computation of the average annual soil loss for the considered basins. In fact, this new information in addition to the observed SSY at the dam’s reservoirs, was used to define a dataset of observed values of Sediment Delivery Ratio (SDR). Consequently, a multiple linear regression analysis was applied by selecting and employing a set of 12 predictive variables suitable for profiling the basins. Specifically, the two samples used in the multiple linear regression analysis comprise respectively the basins geographically located in the Alps and those in the Appennines
Opere di scarico e presa per dighe, traverse e canali
No full textVengono trattate le opere di scarico, presa ed intercettazione per dighe, traverse e canali, con particolare riferimento ai serbatoi: capacità, regolate, al servizio di vari tipi d’utenza produttiva o della laminazione delle piene. L’esame riguarda i differenti tipi di scarico: di superficie, di fondo e mezzofondo e di esaurimento; e, successivamente, le opere di presa sia per uso civile (acquedottistico ) che per uso irriguo ed industriale.
La rassegna è completata da alcuni esempi di organi di scarico e di presa: in qualche caso con applicazioni numeriche.
Il testo fa riferimento anche allo schema di Regolamento per la disciplina del procedimento di approvazione dei progetti e del controllo sulla costruzione e l'esercizio degli sbarramenti
di ritenuta (dighe e traverse) e alla proposta di Aggiornamento delle norme tecniche per la progettazione e la costruzione degli sbarramenti di ritenuta (dighe e traverse);
lo schema e la proposta dovrebbero sostituire a breve il vigente Regolamento Dighe del 1959 e le Norme Tecniche del 1982, nonché le successive Leggi e Circolari
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