119,456 research outputs found
ALTERED EXPRESSION AND FUNCTIONALITY OF A2A ADENOSINE RECEPTORS IN HUNTINGTON’S DISEASE AND OTHER POLYGLUTAMINE DISORDERS
No full textSeveral studies have suggested the possible involvement of A2A adenosine receptors in the
pathogenesis of neuronal disorders, including Huntington’s disease. Huntington’s disease is an
inherited neurodegenerative disease clinically characterized by motor, cognitive and behavioural
impairments. The genetic cause of the disease is the expanded CAG triplet in a gene coding for
huntingtin, a protein involved in several physiological processes. Huntington’s disease affects
primarly GABAergic neurons in the basal ganglia that express adenosine A2A and dopamine D2
receptors. The present study describes a functional alteration of A2A adenosine receptor in striatal
cells engineerized to express full length or truncated, wild type or mutant huntingtin. The data
obtained demonstrate that the presence of mutant huntingtin induce an amplification of the
transduction signal mediated by adenylyl cyclase and an aberrant coupling of A2A receptor to this
transduction pathway. The expression and functionality of A2A adenosine receptor were
subsequently evaluated in transgenic mice R6/2, an animal model of Huntington’s disease that
express exon 1 of the human huntingtin gene. Saturation binding experiments revealed an increase
of A2A receptor levels in striatum of R6/2 mice until 14 post natal days. In addition, also the potency
of a typical A2A agonist was increased in striatal membranes of R6/2 mice when compared to wild
type mice. The subsequent study aimed the evaluation of the presence and functionality of A2A
adenosine receptors in peripheral blood cells from patients affected by Huntington’s disease
compared with control subjects. The results revealed a statistically significant increase of the A2A
receptor density in platelets, lymphocytes and neutrophils of Huntington’s disease patients and presymptomatic
carriers of the mutation when compared to control subjects. In order to verify the
specificity of A2A receptor alteration in polyglutamine disease, the same study was conducted in
blood cells from patients affected by Spinocerebellar ataxia, characterized by an expanded CAG
triplet in the ataxin gene and in patients affected by Friedreich’s ataxia, characterized by an
expansion of the GAA triplet. Saturation binding experiments in peripheral blood cells from
Spinocerebellar ataxia showed altered A2A binding parameters similar to those obtained in
Huntington’s disease patients. In addition, data obtained in Friedreich’s ataxia patients showed
affinity and density values for A2A receptors similar to those obtained from control subjects,
demonstrating the involvement of the CAG but not of the GAA triplet. Overall these data
demonstrate that an aberrant A2A receptor phenotype is present in polyglutamine disorders and this
seems to be related with the expanded CAG triplet. The amplification of the signal transduction
system of A2A receptors suggests that the use of selective A2A antagonists could be beneficial in the
treatment of Huntington’s disease as well as in other related polyglutamine diseases. In addition, the
alteration of A2A receptors in peripheral blood cells of patients with polyglutamine diseases
suggests that this receptor could be an easily accessible biomarker for the evaluation of the efficacy
of potential new therapies
Lezioni di fondamenti e tecnica della progettazione meccanica
No full textIn questo volume sono raccolte le lezioni tenute dal Prof. Dario Croccolo negli insegnamenti di Fondamenti di Progettazione ed Ingegnerizzazione di Prodotto L e di Tecnica delle costruzioni meccaniche L attivati, rispettivamente, presso i Corsi di Laurea in Ingegneria Gestionale ed Ingegneria Meccanica della prima e della seconda Facoltà di Ingegneria dell’Università degli Studi di Bologna.
Tale raccolta è stata concepita e realizzata con l’intento di ampliare i lucidi proiettati in aula e di facilitare la preparazione delle prove d’esame. A tal fine sono stati, perciò, sviluppati ed approfonditi gli argomenti affrontati a lezione senza, però, avere la pretesa di offrirne una trattazione completa per la quale si rimanda ai testi indicati in bibliografia. I contenuti dell’opera sono stati più volte controllati ed aggiornati al fine di adattarli alla recente riforma degli Ordinamenti e dei Regolamenti Universitari e, dunque, le lezioni teoriche curate dal Prof. Croccolo sono state arricchite da molti esempi e calcoli eseguiti anche con metodi numerici agli elementi finiti, curati dall’Ing. Vincenzi, al fine di migliorare la comprensione degli argomenti e rendere il volume il più possibile moderno ed allineato con i recenti strumenti e metodi di calcolo.
Poiché i contenuti fanno riferimento a due insegnamenti di base offerti in Corsi di Studio differenti (Laurea in Ingegneria Meccanica ed in Ingegneria Gestionale) potranno esservi parti di programma già proposte in altri insegnamenti del Corso di Laurea in Ingegneria Meccanica oppure che non saranno mai affrontate e trattate a lezione per il corso di Laurea in Ingegneria Gestionale; in ogni caso tutti gli argomenti, pur essendo tra loro correlati, sono fruibili indipendentemente e, dunque, possono essere compresi e studiati dagli studenti di entrambi i corsi, soprattutto se decidano di frequentare e seguire le lezioni.
Tutti i risultati numerici sono stati arrotondati per eccesso o per difetto in modo da rimanere sempre a favore di sicurezza e da ottenere cifre significative che possiedono valore ingegneristico
Improving the speed performance of an Evolutionary Algorithm by a second-order cost function approximation
No full textIn the present paper, dynamic identification problem of a FE structure with unknown parameters is solved by global search method. Response surface methodology is introduced in Differential Evolution algorithm to improve the performance of the algorithm. Differential evolution (DE) is an evolutionary algorithm where N different vectors collecting the parameters of the system are chosen randomly or by adding weighted differences between vectors obtained from two populations. In the modified algorithm, the new parameter vector is defined as the minimum of a second-order polynomial surface, approximating the cost function. Performance in term of speed rate is strongly improved by introducing the second-order approximation; nevertheless, robustness of DE algorithm for global minimum search of cost function is preserved, since multiple search points are used simultaneously. A numerical examples is presented, concerning identification of mechanical parameters of a steel truss girder bridge with unknown values of masses and stiffnesses of bracing and bearing
Comparison between global optimization algorithms in structural damage assessment
No full textIn the paper, two global optimization techniques (Coupled Local Minimizers method and the Differential Evolution Algorithm) are compared in a benchmark problem. The challenge is to find, by FE model updating, the crack locations and widths, the latter being related to the flexural spring stiffness used to model the crack. The effectiveness of the two algorithms to find the set of optimization parameters has been compared by performing a statistical analysis of the optimization results
Limitation of continuous monitoring via TDR and EC in silty loamy soils to quantify groundwater recharge rates
No full textGroundwater recharge is one of the key factor of the
hydrological budget. Many methods could be used to have
reasonable estimates of this parameter like the water-balance
method, the water table fluctuation method or via numerical
simulations (NIMMO et alii, 2005). Usually these methods are
valid for watershed studies but need to be validated for site
specific applications. Tracer techniques for recharge
assessment are often time consuming and their laboratory costs
are quite elevated. A relatively cheap solution is to employ low
cost TDR probes to monitor the water content and the soil
electrical conductivity (NOBORIO et alii, 2001; MORTL et alii,
2011). The aim of this study is to evaluate the limitation of
continuous monitoring in determining groundwater recharge
rates in agricultural silty soils
Impacts of a railway tunnel on the streams baseflow verified by means of numerical modelling
No full textThe high-speed railway line between Bologna and Florence (Italy) is mostly developed underground through the Tuscan-Emilian Apennine, and the tunnels severely impacted groundwater and surface water. The 15-km-long Firenzuola tunnel crosses siliciclastic turbidites: during drilling, water inrushes occurred at fault and fracture zones, and the tunnel continues to drain the aquifer. The water table dropped below the level of the valleys, and gaining streams transformed into losing streams or ran completely dry, as did many springs. Hydrological observations and two multitracer tests have previously characterized the stream-tunnel connections and the impact processes. In the framework of planning mitigation strategies to minimize impacts on stream baseflow, three-dimensional numerical modelling with MODFLOW (the EPM approach) is applied to evaluate the artificial minimum flow needed to maintain flow continuity along the stream during the recession phase. The establishment of the two presented models is based on hydrogeological monitoring data and the results of flow measurements and tracer tests. Maximum flow rates subtracted from stream baseflow by the tunnel along the connection structures are calculated for two streams with major impacts
Parameter Calibration of a Social Force Model for the Crowd-Induced Vibrations of Footbridges
No full textA reliable prediction of the human-induced vibrations of footbridges relies on an accurate representation of the pedestrian excitation for different loading scenario. Particularly, the modeling of crowd-induced dynamic loading is a critical issue for the serviceability assessment of footbridges. At the design stage, the modeling of crowd loading is often derived from single pedestrian models, neglecting the effect of the structural vibrations as well as the interactions among pedestrians. A detailed description of the crowd behavior can be achieved employing a social force model that describes the different influences affecting individual pedestrian motion. These models are widely adopted to describe the crowd behavior especially in the field of evacuation of public buildings, public safety and transport station management while applications in the serviceability assessment of footbridges are less common. To simulate unidirectional pedestrian flows on footbridges, this paper proposes a parameter calibration of the Helbing’s social force model performed adopting the response surface methodology. Parameters of the social force model are calibrated so as to represent the fundamental relation between mean walking speed and density of the pedestrian crowd. The crowd-induced vibrations are then simulated by modeling each pedestrian in the crowd as a vertical load that crosses the footbridge with time varying trajectory and velocity estimated from the calibrated social force model. Finally, results are compared to those obtained from a multiplication factor approach proposed in literature. This considers the crowd as a uniform distribution of pedestrians with constant speed and given synchronization level and the footbridge response is evaluated as the response to a single pedestrian scaled by a proper enhancement factor
Identificazione strutturale di una struttura metallica mediante prove di vibrazione forzata
No full textNella presente nota si riporta un esempio applicativo di una metodologia di identificazione basata su prove di vibrazione forzata. Vengono descritti i risultati di una prova dinamica con vibrodina effetuata su una porzione dell’ampliamento del Politecnico di Torino a struttura metallica: dai dati sperimentali si sono calcolate le funzioni di risposta in frequenza che hanno fornito frequenze proprie e deformate modali. Successivamente si è confrontata la risposta con un modello agli elementi finiti correlando modi propri e frequenze
Modellazione numerica per la mitigazione degli impatti sul deflusso di base di torrenti appenninici indotti dalle gallerie Alta Velocità
No full textFlutuação estacional das principais especies componentes de pastagem naturalizada sobre-semeada com Lotus Corniculatus L. e submetida a dois tempos de repouso em pastoreio racional voisin em Florianopolis, SC
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias, Programa de Pós-Graduação em Agroecossistemas, Florianópolis, 1998Pressupondo que o manejo influi na composição botânica, introduziu-se por sobre-semeadura o Lotus corniculatus em pastagem naturalizada perene de verão, manejada em dois tempos de repouso em Pastoreio Racional Voisin, com o objetivo de verificar os seus efeitos sobre a flutuação estacional das principais espécies e a possibilidade do melhoramento da pastagem
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