86,658 research outputs found
Finite element analysis of fluid phase nonlinearity effects on the undrained dynamic behaviour of nearly saturated porous media
No full textA simple time integration scheme is presented, able to take into account a particular nonlinearity of the fluid phase in a dynamically loaded, nearly saturated porous medium. The analysis is
confined to the dynamic undrained case, under the assumptions of small displacements and linear elastic behaviour for the solid phase. A mixed finite element approach is adopted, in conjunction with an explicit time integration scheme. The resulting overall algorithm may be theoretically framed within the context of the Linear Inequalities. Some applications indicate that the nonlinear behaviour of the fluid phase alone may play an important role in the global two-phase medium response. The results obtained by means of more traditional approaches in some cases may be un conservative
Double polarisation observable E and helicity dependent cross section for single
No full textPhoton-induced reactions, like meson photoproduction, allow to excite the nucleon, to have access to many different polarisation observables and are an essential tool to disentangle the role of the different electromagnetic multipoles due to the change of sign of some contributions and the presence of interference terms between different multipole amplitudes. In addition, the use of polarised beams and/or targets allow to access additional observables which are fundamental in order to accurately determine the nucleon resonance properties. The A2@MAMI collaboration is carrying out a broad and systematic study on this topics, both on the proton and the neutron. The experiments are performed at the tagged photon beam facility of the MAMI accelerator in Mainz, using circularly and linearly polarised photons on longitudinally polarised proton and deuteron targets, for energies ranging from the pion production threshold up to 1.6 GeV. Hadronic reaction products are then measured with the large acceptance Crystal Ball spectrometer, complemented by charged particle and vertex detectors for tracking and identification. An overview of the results obtained so far for the double polarisation observable E (circularly polarised photon beam on a longitudinally polarised target) on the single π0 photoproduction off the proton and the neutron will be given. Furthermore, new results on the helicity-dependent total and differential cross sections on the deuteron will be presented
Application of numerical procedures to slope stability analysis
No full textthe limit equilibrium procedures based on the assumption of rigid, perfectly plastic material behaviour, and b) the
elasto-plastic approaches. The methods belonging to the first group provide only an estimation of the collapse load
for the slope, while those of the second group are able to evaluate the progressive deformation of the soil/rock mass,
and the variation of effective and neutral stresses, up to failure.
Advantages and shortcomings of the two mentioned classes of procedures will be discussed with reference to engineering
problems and/or case histories. After presenting an application oflimit equilibrium methods to the analysis
of a reinforced earth wall, the discussion is focused on the elasto-plastic finite element approaches and, in particular,
on the choice of the constitutive model for the soil/rock mass
A parsimonious mechanistic model of reproductive and vegetative growth in fruit trees predicts consequences of fruit thinning and branch pruning
No full textProductivity of fruit tree crops depends on the interaction between plant physiology, environmental conditions and agricultural practices. We develop a mechanistic model of fruit tree crops that reliable simulates the dynamics of variables of interest for growers and consequences of agricultural practices while relying on a minimal number of inputs and parameters. The temporal dynamics of carbon content in the different organs (i.e., shoots-S, roots-R and fruits-F) are the result of photosynthesis by S, nutrient supply by R, respiration by S, R and F, competition among different organs, photoperiod and initial system conditions partially controlled by cultural practices. We calibrate model parameters and evaluate model predictions using unpublished data from a peach (Prunus persica) experimental orchard with trees subjected to different levels of branch pruning and fruit thinning. Fiinally, we evaluate the consequences of different combinations of pruning and thinning intensities within a multi-criteria analysis. The predictions are in good agreement with the experimental measurements and for the different conditions (pruning and thinning). Our simulations indicate that thinning and pruning practices actually used by growers provide the best compromise between total shoot production, which impacts next year's abundance of shoots and fruits, and current year's fruit production in terms of quantity (yield) and quality (average fruit size). This suggests that growers are not only interested in maximizing current year's yield but also in its quality and its durability. The present work provides for modelers a system of equations based on acknowledged principles of plant science easily modifiable for different purposes. For horticulturists, it gives insights on the potentialities of pruning and thinning. For ecologists, it provides a transparent quantitative framework that can be coupled with biotic and abiotic stressors
La Commenda di San Tomaso di Majano (UD). Lo scavo archeologico di un ospitale medievale nel contesto del recupero architettonico del complesso
No full textStructural and functional studies of cytosolic 5’-nucleotidase II (cN-II)
No full textLa 5’-nucleotidasi citosolica II (cN-II) è una proteina enzimatica citosolica dalla doppia natura catalitica che fosfoidrolizza i nucleosidi monofosfati purinici con particolare affinità per IMP e GMP. cN-II contribuisce a ripristinarne i livelli catalizzando la formazione di un nuovo nucleoside monofosfato in presenza di un nucleoside accettore a cui viene trasferita la molecola di fosfato che durante la catalisi di fosfoidrolizzazione rimane legata alla forma intermedia dell’ enzima. Per queste ed altre sue proprietà, discusse in abbondanza nel mio lavoro di tesi, nel corso degli anni, cN-II ha attirato l’attenzione della comunità scientifica che ha affrontato lo studio della stessa da numerosi punti di vista quali la biochimica, la cristallografia, la biologia molecolare, l’oncologia, la farmacologia e la genetica. Ad oggi si ha una discreta conoscenza delle proprietà catalitiche, della distribuzione tissutale e dell’abbondanza relativa, nonchè dei principali ruoli fisiologici che caratterizzano cN-II. L’enzima, infatti, appare espresso in maniera ubiquitaria sempre a basse concentrazioni, ad eccezione di quei tessuti altamente rigenerativi e di cellule maligne. Ne è stato accertato, anche, il ruolo chiave nel mantenere l’omeostasi di IMP, precursore di tutti i nucleotidi purinici. Inoltre numerose evidenze si sono accumulate in merito al probabile ruolo cruciale che l’enzima riveste nell’ interferire con l’attivazione di numerosi farmaci usati per contrastare la proliferazione di cellule tumorali laddove è emersa o un’espressione maggiore sia della proteina che del suo prodotto di trascrizione o forme mutate dell’enzima che lo rendono iperattivo. Tale mole di informazioni, sebbene eterogenea e ancora di difficile lettura certa, ha indotto la comunità scientifica a proporre di considerare cN-II come un potenziale target farmacologico. Per questo, numerosi sforzi si stanno compiendo per meglio definire, a lato di ciò che si sa già, il/i ruolo/i fisiologici mediati dalla cN-II, cosi da poter meglio capire per quali motivi tale proteina risulti essere enigmatica nell’ insorgenza di fenomeni di resistenza alle comuni terapie antitumorali che si avvalgono prevalentemente di analoghi nucleosidici come antimetaboliti in grado di bloccare la proliferazione cellulare maligna. In questo contesto si inserisce il mio lavoro di tesi dottorale che nell’arco dei tre anni in cui si è svolto mi ha visto lavorare a cavallo tra due gruppi di ricerca: il gruppo della Pr.ssa Maria Grazia Tozzi presso l’unità di Biochimica del dipartimento di biologia dell’ Università di Pisa e il gruppo del Pr. Charles Dumontet, sotto la supervisone del Dr. Lars Petter Jordheim, presso il Cancer Research Centre di Lione. Nella tesi che segue ho cercato dunque di meglio definire l’impatto che l’ enzima ha sul metabolismo dei nucleotidi intracellulari avvalendomi di modelli cellulari in cui l’espressione di cN-II potesse essere sia stabilmente che inducibilmente alterata. Ho utilizzato poi questi modelli per investigare gli effetti di tali alterazioni e ho cercato di porli al centro del problema dell’ insorgenza dei fenomeni di resistenza farmacologica sopra menzionati. Parallelamente ho affrontato studi in vitro di carattere biochimico con l’intento di definire la relazione tra analoghi di adenosina di prima e seconda generazione e cN-II. Inoltre ho ampliato il mio punto di vista investigativo cercando possibili interattori proteici cellulari che potessero indicare nuove vie di studio verso la conoscenza del complesso scenario in cui la cN-II si inserisce. Quello che è emerso dai miei studi è che l’ espressione di cN-II risulta critica per il mantenimento dell’omeostasi non del solo di IMP ma di molti altri nucleosidi e soprattutto nucleotidi intracellulari. Inoltre simili risposte in diversi modelli hanno confermato un ruolo chiave sia dell’ espressione che dell’ attività dell’ enzima nella proliferazione cellulare e hanno evidenziato non solo le già note correlazioni con fenomeni di resistenza all’ effetto di nucleosidi analoghi ma altresì hanno evidenziato interferenze con altre categorie antimetaboliche farmaceutiche. In aggiunta, tra gli analoghi di adenosina, è stato identificato un ruolo inibitore e interattore della fludarabina rispetto a cN-II che ha fornito delucidazioni sul meccanismo di azione citotossica del farmaco, prima non noto, e che ha posto le basi per considerare di testare la fludarabina, in quanto inibitore di un potenziale target farmacologico, in associazione ad altri farmaci in terapie farmacologiche sinergiche. Per quanto riguarda l’ indagine di possibili interattori di cN-II, è stata accertata un’ evidente e fisiologica relazione di interazione tra cN-II e Ipaf, proteina che riveste un ruolo chiave nei meccanismi immunitari innati. Tale interazione ha posto le basi per lo studio, d’ora in avanti, di cN-II come proteina regolativa di importanti fenomeni cellulari, quali l’ infiammazione e conseguente apoptosi mediata dai recettori del sistema immunitario innato. In conclusione, i risultati del lavoro mio e dei miei colleghi sono stati in parte pubblicati su riviste internazionali: S. Allegrini, D.N. Filoni, A. Galli, A. Collavoli, R. Pesi, M.G. Tozzi (2013) Expression of Bovine Cytosolic 5′-Nucleotidase (cN-II) in Yeast: Nucleotide Pools Disturbance and Its Consequences on Growth and Homologous Recombination. Plos One. 8: e63914. doi: 10.1371/journal.pone.0063914; F. Cividini, R. Pesi, L. Chaloin, S. Allegrini, M. Camici, C. Dumontet, L.P. Jordheim and M.G. Tozzi (2015) The purine analogue fludarabine acts as a cytosolic 5’-nucleotidase II inhibitor. Biochemical Pharmacology. doi:10.1016/j.bcp.2015.01.010; F. Cividini, S. M.G. Tozzi, A. Galli, R. Pesi, M. Camici, C .Dumontet, L.P. Jordheim and S. Allegrini (2015) Cytolosolic 5’-nucleotidase II interacts with the leucin rich repeats of NLR family member Ipaf. Plos One. doi: 10.1371/journal.pone.0121525; ed in parte proposti ma non ancora accettati: F. Cividini, C. Machon, R. Pesi, S. Allegrini, M. Camici, C. Dumontet, L.P. Jordheim and M.G. Tozzi. Stable modulation of cytosolic 5’-nucleotidase II in human glioblastoma ADF cells is associated with modified cell proliferation rate and sensitivity to anticancer agents. Submitted; F. Cividini, D.N. Filoni, R. Pesi, S. Allegrini, M. Camici, M.G. Tozzi. IMP-GMP specific 5’-nucleotidase regulates energy charge and prodrug metabolism. Submitted
On the evaluation of local response spectra according to the Italian design code
No full textThe definition of a seismic action for the structural re-analysis of existing buildings requires generally consists in the assignment of a response spectrum. The Italian design code offers a simplified procedure to account for amplification effects from site conditions. However, when considering cultural heritage buildings a more accurate determination of the local spectrum could be of interest, given the need to effectively protect these assets and the restoration principles and the consequent conservation requirements that impose strict limitations to interventions that may be performed.
The main aspects of the procedure adopted for the evaluation of local response spectra are here recalled, and results are presented for three sites having different stratigraphic conditions and hosting museum buildings. Finally, the results from the simplified procedure and from a complete geophysical analysis are compared
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
Cell proliferation and drug sensitivity of human glioblastoma cells are altered by the stable modulation of cytosolic 5′-nucleotidase II
No full textCytosolic 5'-nucleotidase II (cN-II) has been reported to be involved in cell survival, nucleotide metabolism and in the cellular response to anticancer drugs. With the aim to further evaluate the role of this enzyme in cell biology, we stably modulated its expression the human glioblastoma cell ADF in which the transient inhibition of cN-II has been shown to induce cell death. Stable cell lines were obtained both with inhibition, obtained with plasmids coding cN-II-targeting short hairpin RNA, and stimulation, obtained with plasmids coding Green Fluorescence Protein (GFP)-fused wild type cN-II or a GFP-fused hyperactive mutant (GFP-cN-II-R367Q), of cN-II expression. Silenced cells displayed a decreased proliferation rate while the over expressing cell lines displayed an increased proliferation rate as evidenced by impedance measurement using the xCELLigence device. The expression of nucleotide metabolism relevant genes was only slightly different between cell lines, suggesting a compensatory mechanism in transfected cells. Cells with decreased cN-II expression were resistant to the nucleoside analog fludarabine confirming the involvement of cN-II in the metabolism of this drug. Finally, we observed sensitivity to cisplatin in cN-II silenced cells and resistance to this same drug in cN-II over-expressing cells indicating an involvement of cN-II in the mechanism of action of platinum derivatives, and most probably in DNA repair. In summary, our findings confirm some previous data on the role of cN-II in the sensitivity of cancer cells to cancer drugs, and suggest its involvement in other cellular phenomenon such as cell proliferation
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