1,720,987 research outputs found
Thresholds, long delays and stability from generalized allosteric effect in protein networks
No full textPost-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation are well known to play a pivotal role in the intracellular transduction of activation and death signals. A protein can have multiple sites where chemical groups can reversibly attach in processes such as phosphorylation or nitrosylation. A microscopic description of these processes must take into account the intrinsic probabilistic nature of the underlying reactions. We apply combinatorial considerations to standard enzyme kinetics and in this way we extend to the dynamic regime a simplified version of the traditional models on the allosteric regulation of protein functions. We link a generic modification chain to a downstream Michaelis–Menten enzymatic reaction and we demonstrate numerically that this accounts both for thresholds and long time delays in the conversion of the substrate by the enzyme. The proposed mechanism is stable and robust and the higher the number of modification sites, the greater the stability. We show that a high number of modification sites converts a fast reaction into a slow process, and the slowing down depends on the number of sites and may span many orders of magnitude; in this way multisite modification of proteins stands out as a general mechanism that allows the transfer of information from the very short time scales of enzyme reactions (milliseconds) to the long time scale of cell response (hours)
Crescita dei tumori solidi: un approccio multidisciplinare che attraversa la fenomenologia e la modellizzazione biofisica per approdare alla clinica
No full textFractional momentum correlations in multiparton collisions at LHC
No full textMultiple parton collisions will represent a rather common feature in pp collisions at the LHC, where regimes with very large momentum transfer may be studied and events rare in lower energy accelerators might occur with a significant rate. A reason of interest in large pt regimes is that, differently from low pt, evolution will induce correlations in x in the multiparton structure functions. We have estimated the cross section of multiple production of W bosons with equal sign, where the correlations in x induced by evolution are particularly relevant, and the cross section of View the MathML source production, where the effects of evolution are much smaller
Precision and stability issues in VBL, the Virtual Biophysics Lab simulation program
No full textThe network of biochemical reactions inside living organisms is characterized by an overwhelming complexity which stems from the sheer number of reactions and from the complicated topology of biochemical cycles. However the high speed of computers and the sophisticated computational methods that are available today are powerful tools that allow the numerical exploration of these exceedingly interesting dynamical systems. We are now developing a program that simulates tumor spheroids (VBL, Virtual Biophysics Lab), and which includes a reduced – but still quite complex – description of the biochemistry of individual cells, plus many diffusion processes that bring oxygen and nutrients into cells and metabolites into the environment. Each simulation step requires the integration of nonlinear differential equations that describe the individual cell's clockwork and the integration of the diffusion equations. These integrations are carried out under widely different conditions, in a changing environment, and for this reason they need integrators that are both unconditionally stable and that do not display unwanted algorithmic artifacts. These conditions are not always fulfilled in the existing literature, and we feel that a review of the underlying mathematical principles may be important not just for us but for other workers in the field of system biology as well
Dynamics of intracellular Ca^{2+} oscillations in the presence of multisite Ca^{2+}-binding proteins
No full textWe study the dynamics of intracellular calcium oscillations in the presence of proteins that bind calcium on multiple sites and that are generally believed to act as passive calcium buffers in cells. These multisite calcium-binding proteins set a sharp threshold for calcium oscillations, and calcium oscillations stop at high concentrations of calcium-binding proteins. However even in these adverse conditions, internal noise, which shows up spontaneously in cells in the process of calcium wave formation, can lead to self-oscillations. This produces oscillatory behaviors strikingly similar to those observed in real cells. In addition, for given intracellular concentrations of both calcium and calcium-binding proteins the regularity of these oscillations changes and reaches a maximum as a function of the noise variance, and we find that the overall system dynamics displays coherence resonance. Thus it turns out that the calcium-binding proteins can have an important and non-trivial regularizing role
L’offerta di servizi di trasporto pubblico a lunga percorrenza: Connettere i territori intermedi e non dimenticare i margini
No full text"Produrre conoscenza utizzabile: il ruolo civile dell'università per i territori fragili"
No full textStrategie territoriali. Percorsi possibili per attingere al potenziale inespresso dei luoghi
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