Sensory systems adapt, i.e., they adjust their sensitivity to external stimuli according to the ambient level. In this paper we show that single cell electrophysiological responses of vertebrate olfactory receptors and of photoreceptors to different input protocols exhibit several common features related to adaptation, and that these features can be used to investigate the dynamical structure of the feedback regulation responsible for the adaptation. In particular, we point out that two different forms of adaptation can be observed, in response to steps and to pairs of pulses. These two forms of adaptation appear to be in a dynamical trade-off: the more adaptation to a step is close to perfect, the slower is the recovery in adaptation to pulse pairs and viceversa. Neither of the two forms is explained by the dynamical models currently used to describe adaptation, such as the integral feedback model.

1 aDe Palo, Giovanna1 aFacchetti, Giuseppe1 aMazzolini, Monica1 aMenini, Anna1 aTorre, Vincent1 aAltafini, Claudio uhttps://www.math.sissa.it/publication/common-dynamical-features-sensory-adaptation-photoreceptors-and-olfactory-sensory01988nas a2200133 4500008004100000245010500041210006900146260003000215520151100245100002101756700002201777700001901799856003601818 2013 en d00aEarly phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus0 aEarly phase of plasticityrelated gene regulation and SRF depende bPublic Library of Science3 aHippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 µM gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10:90] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box.1 aIacono, Giovanni1 aAltafini, Claudio1 aTorre, Vincent uhttp://hdl.handle.net/1963/728701218nas a2200121 4500008004100000245008200041210006900123520080800192100002201000700002301022700001501045856003601060 2013 en d00aStabilization of Stochastic Quantum Dynamics via Open and Closed Loop Control0 aStabilization of Stochastic Quantum Dynamics via Open and Closed3 aIn this paper, we investigate parametrization-free solutions of the problem of quantum pure state preparation and subspace stabilization by means of Hamiltonian control, continuous measurement, and quantum feedback, in the presence of a Markovian environment. In particular, we show that whenever suitable dissipative effects are induced either by the unmonitored environment, or by non-Hermitian measurements, there is no need for feedback, as open-loop time-invariant control is sufficient to achieve stabilization of the target set in probability. Constructive necessary and sufficient conditions on the form of the control Hamiltonian can be provided in this case. When time-invariant control is not sufficient, state stabilization can be attained by the addition of filtering-based feedback control1 aAltafini, Claudio1 aTicozzi, Francesco1 aNishio, K. uhttp://hdl.handle.net/1963/650301414nas a2200145 4500008004100000245008300041210006900124260002800193520092600221100002001147700002201167700002101189700002201210856003601232 2012 en d00aDecompositions of large-scale biological systems based on dynamical properties0 aDecompositions of largescale biological systems based on dynamic bOxford University Press3 aMOTIVATION: Given a large-scale biological network represented as an influence graph, in this article we investigate possible decompositions of the network aimed at highlighting specific dynamical properties.\\r\\nRESULTS: The first decomposition we study consists in finding a maximal directed acyclic subgraph of the network, which dynamically corresponds to searching for a maximal open-loop subsystem of the given system. Another dynamical property investigated is strong monotonicity. We propose two methods to deal with this property, both aimed at decomposing the system into strongly monotone subsystems, but with different structural characteristics: one method tends to produce a single large strongly monotone component, while the other typically generates a set of smaller disjoint strongly monotone subsystems.\\r\\nAVAILABILITY: Original heuristics for the methods investigated are described in the article.1 aSoranzo, Nicola1 aRamezani, Fahimeh1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/522602153nas a2200181 4500008004100000245015200041210006900193260001000262520154500272100001101817700002101828700001601849700001501865700001401880700001901894700002201913856003601935 2012 en d00aDetection of transcriptional triggers in the dynamics of microbial growth: application to the respiratory-versatile bacterium Shewanella oneidensis0 aDetection of transcriptional triggers in the dynamics of microbi bSISSA3 aThe capacity of microorganisms to respond to variable external conditions requires a coordination of environment-sensing mechanisms and decisionmaking regulatory circuits. Here, we seek to understand the interplay between these two processes by combining high-throughput measurement of time-dependent mRNA profiles with a novel computational approach that searches for key genetic triggers of transcriptional changes. Our approach helped us understand the regulatory strategies of a respiratorily versatile bacterium with promising bioenergy and bioremediation applications, Shewanella oneidensis, in minimal and rich media. By comparing expression profiles across these two conditions, we unveiled components of the transcriptional program that depend mainly on the growth phase. Conversely, by integrating our time-dependent data with a previously available large compendium of static perturbation responses, we identified transcriptional changes that cannot be explained solely by internal network dynamics, but are rather triggered by specific genes acting as key mediators of an environment-dependent response. These transcriptional triggers include known and novel regulators that respond to carbon, nitrogen and oxygen limitation. Our analysis suggests a sequence of physiological responses, including a coupling between nitrogen depletion and glycogen storage, partially recapitulated through dynamic flux balance analysis, and experimentally confirmed by metabolite measurements. Our approach is broadly applicable to other systems1 aBeg, Q1 aZampieri, Mattia1 aKlitgord, N1 aCollins, S1 aSerres, M1 aSegrè, Daniel1 aAltafini, Claudio uhttp://hdl.handle.net/1963/650601693nas a2200157 4500008004100000245008400041210006900125260003400194520117300228100002201401700002001423700001701443700001701460700002201477856003601499 2012 en d00aA dynamical feedback model for adaptation in the olfactory transduction pathway0 adynamical feedback model for adaptation in the olfactory transdu bBiophysical Society, Elsevier3 aOlfactory transduction exhibits two distinct types of adaptation, which we denote multipulse and step adaptation. In terms of measured transduction current, multipulse adaptation appears as a decrease in the amplitude of the second of two consecutive responses when the olfactory neuron is stimulated with two brief pulses. Step adaptation occurs in response to a sustained steplike stimulation and is characterized by a return to a steady-state current amplitude close to the prestimulus value, after a transient peak. In this article, we formulate a dynamical model of the olfactory transduction pathway, which includes the kinetics of the CNG channels, the concentration of Ca ions flowing through them, and the Ca-complexes responsible for the regulation. Based on this model, a common dynamical explanation for the two types of adaptation is suggested. We show that both forms of adaptation can be well described using different time constants for the kinetics of Ca ions (faster) and the kinetics of the feedback mechanisms (slower). The model is validated on experimental data collected in voltage-clamp conditions using different techniques and animal species.1 aDe Palo, Giovanna1 aBoccaccio, Anna1 aMiri, Andrew1 aMenini, Anna1 aAltafini, Claudio uhttp://hdl.handle.net/1963/701901344nas a2200109 4500008004100000245007300041210006900114260000900183520098400192100002201176856003601198 2012 en d00aDynamics of opinion forming in structurally balanced social networks0 aDynamics of opinion forming in structurally balanced social netw bPLoS3 aA structurally balanced social network is a social community that splits into two antagonistic factions (typical example being a two-party political system). The process of opinion forming on such a community is most often highly predictable, with polarized opinions reflecting the bipartition of the network. The aim of this paper is to suggest a class of dynamical systems, called monotone systems, as natural models for the dynamics of opinion forming on structurally balanced social networks. The high predictability of the outcome of a decision process is explained in terms of the order-preserving character of the solutions of this class of dynamical systems. If we represent a social network as a signed graph in which individuals are the nodes and the signs of the edges represent friendly or hostile relationships, then the property of structural balance corresponds to the social community being splittable into two antagonistic factions, each containing only friends.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/605101741nas a2200133 4500008004100000245007700041210006900118260001000187520130700197100002401504700002101528700002201549856003601571 2012 en d00aExploring the low-energy landscape of large-scale signed social networks0 aExploring the lowenergy landscape of largescale signed social ne bSISSA3 aAnalogously to a spin glass, a large-scale signed social network is characterized by the presence of disorder, expressed in this context (and in the social network literature) by the concept of structural balance. If, as we have recently shown, the signed social networks currently available have a limited amount of true disorder (or frustration), it is also interesting to investigate how this frustration is organized, by exploring the landscape of near-optimal structural balance. What we obtain in this paper is that while one of the networks analyzed shows a unique valley of minima, and a funneled landscape that gradually and smoothly worsens as we move away from the optimum, another network shows instead several distinct valleys of optimal or near-optimal structural balance, separated by energy barriers determined by internally balanced subcommunities of users, a phenomenon similar to the replica-symmetry breaking of spin glasses. Multiple, essentially isoenergetic, arrangements of these communities are possible. Passing from one valley to another requires one to destroy the internal arrangement of these balanced subcommunities and then to reform it again. It is essentially this process of breaking the internal balance of the subcommunities which gives rise to the energy barriers.1 aFacchetti, Giuseppe1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/650401486nas a2200121 4500008004100000245006100041210006000102260005400162520106700216100002201283700002301305856003601328 2012 en d00aModeling and control of quantum systems: An introduction0 aModeling and control of quantum systems An introduction bInstitute of Electrical and Electronics Engineers3 aThe scope of this work is to provide a self-contained introduction to a selection of basic theoretical aspects in the modeling and control of quantum mechanical systems, as well as a brief survey on the main approaches to control synthesis. While part of the existing theory, especially in the open-loop setting, stems directly from classical control theory (most notably geometric control and optimal control), a number of tools specifically tailored for quantum systems have been developed since the 1980s, in order to take into account their distinctive features: the probabilistic nature of atomic-scale physical systems, the effect of dissipation and the irreversible character of the measurements have all proved to be critical in feedback-design problems. The relevant dynamical models for both closed and open quantum systems are presented, along with the main results on their controllability and stability. A brief review of several currently available control design methods is meant to provide the interested reader with a roadmap for further studies1 aAltafini, Claudio1 aTicozzi, Francesco uhttp://hdl.handle.net/1963/650502201nas a2200133 4500008004100000245010400041210006900145260001900214520173100233100002401964700002201988700002102010856003602031 2012 en d00aPredicting and characterizing selective multiple drug treatments for metabolic diseases and cancer.0 aPredicting and characterizing selective multiple drug treatments bBioMed Central3 aBackground: In the field of drug discovery, assessing the potential of multidrug therapies is a difficult task because of the combinatorial complexity (both theoretical and experimental) and because of the requirements on the selectivity of the therapy. To cope with this problem, we have developed a novel method for the systematic in silico investigation of synergistic effects of currently available drugs on genome-scale metabolic networks. The algorithm finds the optimal combination of drugs which guarantees the inhibition of an objective function, while minimizing the side effect on the overall network. Results: Two different applications are considered: finding drug synergisms for human metabolic diseases (like diabetes, obesity and hypertension) and finding antitumoral drug combinations with minimal side effect on the normal human metabolism.The results we obtain are consistent with some of the available therapeutic indications and predict some new multiple drug treatments.A cluster analysis on all possible interactions among the currently available drugs indicates a limited variety on the metabolic targets for the approved drugs. Conclusion: The in silico prediction of drug synergism can represent an important tool for the repurposing of drug in a realistic perspective which considers also the selectivty of the therapy. Moreover, for a more profitable exploitation of drug-drug interactions, also drugs which show a too low efficacy but which have a non-common mechanism of action, can be reconsider as potential ingredients of new multicompound therapeutic indications.Needless to say the clues provided by a computational study like ours need in any case to be thoroughly evaluated experimentally.1 aFacchetti, Giuseppe1 aAltafini, Claudio1 aZampieri, Mattia uhttp://hdl.handle.net/1963/651501400nas a2200169 4500008004100000245009000041210006900131260005000200520083200250100001401082700001801096700001501114700002201129700002201151700002101173856003601194 2011 en d00aAdaptation as a genome-wide autoregulatory principle in the stress response of yeast.0 aAdaptation as a genomewide autoregulatory principle in the stres bThe Institution of Engineering and Technology3 aThe gene expression response of yeast to various types of stresses/perturbations shows a common functional and dynamical pattern for the vast majority of genes, characterised by a quick transient peak (affecting primarily short genes) followed by a return to the pre-stimulus level. Kinetically, this process of adaptation following the transient excursion can be modelled using a genome-wide autoregulatory mechanism by means of which yeast aims at maintaining a preferential concentration in its mRNA levels. The resulting feedback system explains well the different time constants observable in the transient response, while being in agreement with all the known experimental dynamical features. For example, it suggests that a very rapid transient can be induced also by a slowly varying concentration of the gene products.1 aEduati, F1 aDi Camillo, B1 aToffolo, G1 aAltafini, Claudio1 aDe Palo, Giovanna1 aZampieri, Mattia uhttp://hdl.handle.net/1963/510601286nas a2200145 4500008004100000245007900041210006900120260003300189520078400222653003101006100002401037700002101061700002201082856003601104 2011 en d00aComputing global structural balance in large-scale signed social networks.0 aComputing global structural balance in largescale signed social bNational Academy of Sciences3 aStructural balance theory affirms that signed social networks (i.e., graphs whose signed edges represent friendly/hostile interactions among individuals) tend to be organized so as to avoid conflictual situations, corresponding to cycles of negative parity. Using an algorithm for ground-state calculation in large-scale Ising spin glasses, in this paper we compute the global level of balance of very large online social networks and verify that currently available networks are indeed extremely balanced. This property is explainable in terms of the high degree of skewness of the sign distributions on the nodes of the graph. In particular, individuals linked by a large majority of negative edges create mostly \\\"apparent disorder,\\\" rather than true \\\"frustration.\\\"10aCombinatorial optimization1 aFacchetti, Giuseppe1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/642601822nas a2200145 4500008004100000245009200041210006900133260002800202520132600230100002101556700002201577700001901599700002201618856003601640 2011 en d00aA system-level approach for deciphering the transcriptional response to prion infection0 asystemlevel approach for deciphering the transcriptional respons bOxford University Press3 aMOTIVATION: Deciphering the response of a complex biological system to an insulting event, at the gene expression level, requires adopting theoretical models that are more sophisticated than a one-to-one comparison (i.e. t-test). Here, we investigate the ability of a novel reverse engineering approach (System Response Inference) to unveil non-obvious transcriptional signatures of the system response induced by prion infection.\\r\\nRESULTS: To this end, we analyze previously published gene expression data, from which we extrapolate a putative full-scale model of transcriptional gene-gene dependencies in the mouse central nervous system. Then, we use this nominal model to interpret the gene expression changes caused by prion replication, aiming at selecting the genes primarily influenced by this perturbation. Our method sheds light on the mode of action of prions by identifying key transcripts that are the most likely to be responsible for the overall transcriptional rearrangement from a nominal regulatory network. As a first result of our inference, we have been able to predict known targets of prions (i.e. PrP(C)) and to unveil the potential role of previously unsuspected genes.\\r\\nCONTACT: altafini@sissa.it\\r\\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.1 aZampieri, Mattia1 aLegname, Giuseppe1 aSegrè, Daniel1 aAltafini, Claudio uhttp://hdl.handle.net/1963/574501148nas a2200133 4500008004100000245009700041210006900138260001300207520069800220100002200918700002200940700001600962856003600978 2010 en d00aFeedback schemes for radiation damping suppression in NMR: a control-theoretical perspective0 aFeedback schemes for radiation damping suppression in NMR a cont bElsevier3 aIn NMR spectroscopy, the collective measurement is weakly invasive and its back-action is called radiation damping. The aim of this paper is to provide a control-theoretical analysis of the problem of suppressing this radiation damping. It is shown that the two feedback schemes commonly used in the NMR practice correspond one to a high gain oputput feedback for the simple case of maintaining the spin 1/2 in its inverted state, and the second to a 2-degree of freedom control design with a prefeedback that exactly cancels the radiation damping field. A general high gain feedback stabilization design not requiring the knowledge of the radiation damping time constant is also investigated.1 aAltafini, Claudio1 aCappellaro, Paola1 aCory, David uhttp://hdl.handle.net/1963/438400781nas a2200121 4500008004300000245008400043210006900127260004800196520033500244100002200579700002200601856003600623 2010 en_Ud 00aA kinetic mechanism inducing oscillations in simple chemical reactions networks0 akinetic mechanism inducing oscillations in simple chemical react bAmerican Institute of Mathematical Sciences3 aIt is known that a kinetic reaction network in which one or more secondary substrates are acting as cofactors may exhibit an oscillatory behavior. The aim of this work is to provide a description of the functional form of such a cofactor action guaranteeing the\\r\\nonset of oscillations in sufficiently simple reaction networks.1 aCoatleven, Julien1 aAltafini, Claudio uhttp://hdl.handle.net/1963/239302106nas a2200121 4500008004300000245013400043210006900177260001900246520164000265100002101905700002201926856003601948 2010 en_Ud 00aMonotonicity, frustration, and ordered response: an analysis of the energy landscape of perturbed large-scale biological networks0 aMonotonicity frustration and ordered response an analysis of the bBioMed Central3 aBackground. \\nFor large-scale biological networks represented as signed graphs, the index of frustration measures how far a network is from a monotone system, i.e., how incoherently the system responds to perturbations.\\nResults. \\nIn this paper we find that the frustration is systematically lower in transcriptional networks (modeled at functional level) than in signaling and metabolic networks (modeled at stoichiometric level). A possible interpretation of this result is in terms of energetic cost of an interaction: an erroneous or contradictory transcriptional action costs much more than a signaling/metabolic error, and therefore must be avoided as much as possible. Averaging over all possible perturbations, however, we also find that unlike for transcriptional networks, in the signaling/metabolic networks the probability of finding the system in its least frustrated configuration tends to be high also in correspondence of a moderate energetic regime, meaning that, in spite of the higher frustration, these networks can achieve a globally ordered response to perturbations even for moderate values of the strength of the interactions. Furthermore, an analysis of the energy landscape shows that signaling and metabolic networks lack energetic barriers around their global optima, a property also favouring global order.\\nConclusion. \\nIn conclusion, transcriptional and signaling/metabolic networks appear to have systematic differences in both the index of frustration and the transition to global order. These differences are interpretable in terms of the different functions of the various classes of networks.1 aIacono, Giovanni1 aAltafini, Claudio uhttp://hdl.handle.net/1963/405502219nas a2200157 4500008004300000245014000043210006900183260001900252520163800271100002601909700002101935700002801956700002201984700001902006856003602025 2009 en_Ud 00aCharacterization of the time course of changes of the evoked electrical activity in a model of a chemically-induced neuronal plasticity0 aCharacterization of the time course of changes of the evoked ele bBioMed Central3 aBACKGROUND: Neuronal plasticity is initiated by transient elevations of neuronal networks activity leading to changes of synaptic properties and providing the basis for memory and learning 1. An increase of electrical activity can be caused by electrical stimulation 2 or by pharmacological manipulations: elevation of extracellular K+ 3, blockage of inhibitory pathways 4 or by an increase of second messengers intracellular concentrations 5. Neuronal plasticity is mediated by several biochemical pathways leading to the modulation of synaptic strength, density of ionic channels and morphological changes of neuronal arborisation 6. On a time scale of a few minutes, neuronal plasticity is mediated by local protein trafficking 7 while, in order to sustain modifications beyond 2-3 h, changes of gene expression are required 8. FINDINGS: In the present manuscript we analysed the time course of changes of the evoked electrical activity during neuronal plasticity and we correlated it with a transcriptional analysis of the underlying changes of gene expression. Our investigation shows that treatment for 30 min. with the GABAA receptor antagonist gabazine (GabT) causes a potentiation of the evoked electrical activity occurring 2-4 hours after GabT and the concomitant up-regulation of 342 genes. Inhibition of the ERK1/2 pathway reduced but did not abolish the potentiation of the evoked response caused by GabT. In fact not all the genes analysed were blocked by ERK1/2 inhibitors. CONCLUSION: These results are in agreement with the notion that neuronal plasticity is mediated by several distinct pathways working in unison.1 aBroccard, Frederic D.1 aPegoraro, Silvia1 aRuaro, Maria Elisabetta1 aAltafini, Claudio1 aTorre, Vincent uhttp://hdl.handle.net/1963/370600997nas a2200109 4500008004300000245011900043210006900162260001300231520058500244100002200829856003600851 2009 en_Ud 00aControllability and simultaneous controllability of isospectral bilinear control systems on complex flag manifolds0 aControllability and simultaneous controllability of isospectral bElsevier3 aFor isospectral bilinear control systems evolving on the so-called complex flag manifolds (i.e., on the orbits of the Hermitian matrices under unitary conjugation action) it is shown that controllability is almost always verified. Easy and generic sufficient conditions are provided. The result applies to the problem of density operator controllability of finite dimensional quantum mechanical systems. In addition, we show that systems having different drifts (corresponding for example to different Larmor frequencies) are simultaneously controllable by the same control field.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/352300980nas a2200121 4500008004300000245005900043210005800102260002800160520059200188100002000780700002200800856003600822 2009 en_Ud 00aERNEST: a toolbox for chemical reaction network theory0 aERNEST a toolbox for chemical reaction network theory bOxford University Press3 aSummary: ERNEST Reaction Network Equilibria Study Toolbox is a MATLAB package which, by checking various different criteria on the structure of a chemical reaction network, can exclude the multistationarity of the corresponding reaction system. The results obtained are independent of the rate constants of the reactions, and can be used for model discrimination.\\nAvailability and Implementation: The software, implemented in MATLAB, is available under the GNU GPL free software license from http://people.sissa.it/~altafini/papers/SoAl09/. It requires the MATLAB Optimization Toolbox.1 aSoranzo, Nicola1 aAltafini, Claudio uhttp://hdl.handle.net/1963/382601588nas a2200133 4500008004300000245010000043210006900143260000900212520113200221100002101353700002201374700002201396856003601418 2009 en_Ud 00aInvestigating the Conformational Stability of Prion Strains through a Kinetic Replication Model0 aInvestigating the Conformational Stability of Prion Strains thro bPLoS3 aPrion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrPSc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils\\\' mean length) and is coherent with all experimental observations concerning strain-specific behavior.1 aZampieri, Mattia1 aLegname, Giuseppe1 aAltafini, Claudio uhttp://hdl.handle.net/1963/398901344nas a2200145 4500008004300000245009700043210006900140260001900209520085100228100002001079700002101099700002001120700002201140856003601162 2009 en_Ud 00amRNA stability and the unfolding of gene expression in the long-period yeast metabolic cycle0 amRNA stability and the unfolding of gene expression in the longp bBioMed Central3 aBackground: In yeast, genome-wide periodic patterns associated with energy-metabolic oscillations have been shown recently for both short (approx. 40 min) and long (approx. 300 min) periods.\\nResults: The dynamical regulation due to mRNA stability is found to be an important aspect of the genome-wide coordination of the long-period yeast metabolic cycle. It is shown that for periodic genes, arranged in classes according either to expression profile or to function, the pulses of mRNA abundance have phase and width which are directly proportional to the corresponding turnover rates.\\nConclusion: The cascade of events occurring during the yeast metabolic cycle (and their correlation with mRNA turnover) reflects to a large extent the gene expression program observable in other dynamical contexts such as the response to stresses/stimuli.1 aSoranzo, Nicola1 aZampieri, Mattia1 aFarina, Lorenzo1 aAltafini, Claudio uhttp://hdl.handle.net/1963/363002210nas a2200121 4500008004300000245009000043210006900133520178700202100002101989700002002010700002202030856003602052 2008 en_Ud 00aDiscerning static and causal interactions in genome-wide reverse engineering problems0 aDiscerning static and causal interactions in genomewide reverse 3 aBackground. In the past years devicing methods for discovering gene regulatory mechanisms at a genome-wide level has become a fundamental topic in the field of system biology. The aim is to infer gene-gene interactions in a more sophisticated and reliable way through the continuously improvement of reverse engineering algorithms exploiting microarray technologies. Motivation. This work is inspired by the several studies suggesting that co-expression is mostly related to \\\"static\\\" stable binding relationships, like belonging to the same protein complex, rather than other types of interactions more of a \\\"causal\\\" and transient nature (metabolic pathway or transcription factor-binding site interaction). Discerning static relationships from causal ones on the basis of their characteristic regulatory structures and in particular identifing \\\"dense modules\\\" with protein complex, and \\\"sparse modules\\\" with causal interactions such as those between transcription factor and corresponding binding site, the performances of different network inference algorithms in artificial and real networks (derived from E.coli and S.cerevisiae) can be tested and compared. Results. Our study shows that methods that try to prune indirect interactions from the inferred gene networks may fail to retrieve genes co-participating in a protein complex. On the other hand they are more robust in the identification of transcription factor-binding sites dependences when multiple transcription factors regulate the expression of the same gene. In the end we confirm the stronger co-expression regarding genes belonging to a protein complex than transcription factor-binding site, according, also, to the effect of multiple transcription factors and a low expression variance.1 aZampieri, Mattia1 aSoranzo, Nicola1 aAltafini, Claudio uhttp://hdl.handle.net/1963/275702183nas a2200133 4500008004300000245010900043210006900152520170600221100002101927700002001948700002301968700002201991856003602013 2008 en_Ud 00aOrigin of Co-Expression Patterns in E.coli and S.cerevisiae Emerging from Reverse Engineering Algorithms0 aOrigin of CoExpression Patterns in Ecoli and Scerevisiae Emergin3 aBackground: The concept of reverse engineering a gene network, i.e., of inferring a genome-wide graph of putative genegene interactions from compendia of high throughput microarray data has been extensively used in the last few years to deduce/integrate/validate various types of \\\"physical\\\" networks of interactions among genes or gene products. Results: This paper gives a comprehensive overview of which of these networks emerge significantly when reverse engineering large collections of gene expression data for two model organisms, E.coli and S.cerevisiae, without any prior information. For the first organism the pattern of co-expression is shown to reflect in fine detail both the operonal structure of the DNA and the regulatory effects exerted by the gene products when co-participating in a protein complex. For the second organism we find that direct transcriptional control (e.g., transcription factor-binding site interactions) has little statistical significance in comparison to the other regulatory mechanisms (such as co-sharing a protein complex, colocalization on a metabolic pathway or compartment), which are however resolved at a lower level of detail than in E.coli. Conclusion: The gene co-expression patterns deduced from compendia of profiling experiments tend to unveil functional categories that are mainly associated to stable bindings rather than transient interactions. The inference power of this systematic analysis is substantially reduced when passing from E.coli to S.cerevisiae. This extensive analysis provides a way to describe the different complexity between the two organisms and discusses the critical limitations affecting this type of methodologies.1 aZampieri, Mattia1 aSoranzo, Nicola1 aBianchini, Daniele1 aAltafini, Claudio uhttp://hdl.handle.net/1963/272202020nas a2200121 4500008004300000245013300043210006900176520155200245100002001797700002301817700002201840856003601862 2007 en_Ud 00aComparing association network algorithms for reverse engineering of large scale gene regulatory networks: synthetic vs real data0 aComparing association network algorithms for reverse engineering3 aMotivation: Inferring a gene regulatory network exclusively from microarray expression profiles is a difficult but important task. The aim of this work is to compare the predictive power of some of the most popular algorithms in different conditions (like data taken at equilibrium or time courses) and on both synthetic and real microarray data. We are in particular interested in comparing similarity measures both of linear type (like correlations and partial correlations) and of nonlinear type (mutual information and conditional mutual information), and in investigating the underdetermined case (less samples than genes). Results: In our simulations we see that all network inference algorithms obtain better performances from data produced with \\\"structural\\\" perturbations, like gene knockouts at steady state, than with any dynamical perturbation. The predictive power of all algorithms is confirmed on a reverse engineering problem from E. coli gene profiling data: the edges of the \\\"physical\\\" network of transcription factor-binding sites are significantly overrepresented among the highest weighting edges of the graph that we infer directly from the data without any structure supervision. Comparing synthetic and in vivo data on the same network graph allows us to give an indication of how much more complex a real transcriptional regulation program is with respect to an artificial model. Availability: Software and supplementary material are freely available at the URL http://people.sissa.it/~altafini/papers/SoBiAl07/1 aSoranzo, Nicola1 aBianconi, Ginestra1 aAltafini, Claudio uhttp://hdl.handle.net/1963/202800760nas a2200097 4500008004300000245003700043210003700080520048700117100002200604856003600626 2007 en_Ud 00aFeedback control of spin systems0 aFeedback control of spin systems3 aThe feedback stabilization problem for ensembles of coupled spin 1/2 systems is discussed from a control theoretic perspective. The noninvasive nature of the bulk measurement allows for a fully unitary and deterministic closed loop. The Lyapunov-based feedback design presented does not require spins that are selectively addressable. With this method, it is possible to obtain control inputs also for difficult tasks, like suppressing undesired couplings in identical spin systems.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/180801194nas a2200097 4500008004300000245010500043210006900148520082100217100002201038856003601060 2007 en_Ud 00aFeedback stabilization of quantum ensembles: a global convergence analysis on complex flag manifolds0 aFeedback stabilization of quantum ensembles a global convergence3 aIn an N-level quantum mechanical system, the problem of unitary feedback stabilization of mixed density operators to periodic orbits admits a natural Lyapunov-based time-varying feedback design. A global description of the domain of attraction of the closed-loop system can be provided based on a \\\"root-space\\\"-like structure of the space of density operators. This convex set foliates as a complex flag manifold where each leaf is identified with the coadjoint orbit of the eigenvalues of the density operator. The converging conditions are time-independent but depend from the topology of the flag manifold: it is shown that the closed loop must have a number of equilibria at least equal to the Euler characteristic of the manifold, thus imposing obstructions of topological nature to global stabilizability.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/172900859nas a2200109 4500008004300000245008400043210006900127520047200196100002200668700002300690856003600713 2006 en_Ud 00aAlmost Global Stochastic Feedback Stabilization of Conditional Quantum Dynamics0 aAlmost Global Stochastic Feedback Stabilization of Conditional Q3 aWe propose several parametrization-free solutions to the problem of quantum state reduction control by means of continuous measurement and smooth quantum feedback. In particular, we design a feedback law for which almost global stochastic feedback stabilization can be proved analytically by means of Lyapunov techinques. This synthesis arises very naturally from the physics of the problem, as it relies on the variance associated with the quantum filtering process.1 aAltafini, Claudio1 aTicozzi, Francesco uhttp://hdl.handle.net/1963/172700866nas a2200097 4500008004300000245013100043210006900174520046700243100002200710856003600732 2006 en_Ud 00aHomogeneous polynomial forms for simultaneous stabilizability of families of linear control systems: a tensor product approach0 aHomogeneous polynomial forms for simultaneous stabilizability of3 aThe paper uses the formalism of tensor products in order to deal with the problem of simultaneous\\nstabilizability of a family of linear control systems by means of Lyapunov functions which are homogeneous polynomial forms. While the feedback synthesis seems to be nonconvex, the simultaneous stability by means of homogeneous polynomial forms of the uncontrollable modes yields (convex) necessary but not sufficient conditions for simultaneous stabilizability.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/222601165nas a2200109 4500008004300000245005900043210005900102520081400161100002200975700002200997856003601019 2006 en_Ud 00aReflection symmetries for multiqubit density operators0 aReflection symmetries for multiqubit density operators3 aFor multiqubit density operators in a suitable tensorial basis, we show that a number of nonunitary operations used in the detection and synthesis of entanglement are classifiable as reflection symmetries, i.e., orientation changing rotations. While one-qubit reflections correspond to antiunitary symmetries, as is known for example from the partial transposition criterion, reflections on the joint density of two or more qubits are not accounted for by the Wigner Theorem and are well-posed only for sufficiently mixed states. One example of such nonlocal reflections is the unconditional NOT operation on a multiparty density, i.e., an operation yelding another density and such that the sum of the two is the identity operator. This nonphysical operation is admissible only for sufficiently mixed states.1 aAltafini, Claudio1 aHavel, Timothy F. uhttp://hdl.handle.net/1963/212101041nas a2200097 4500008004300000245006900043210006900112520070400181100002200885856003600907 2005 en_Ud 00aCommuting multiparty quantum observables and local compatibility0 aCommuting multiparty quantum observables and local compatibility3 aA formula for the commutator of tensor product matrices is used to shows that, for qubits, compatibility of quantum multiparty observables almost never implies local compatibility at each site and to predict when this happens/does not happen in a concise manner. In particular, it is shown that two ``fully nontrivial\\\'\\\' $n$-qubit observables are compatible locally and globally if and only if they are equal up to sign. In addition, the formula gives insight into the construction of new paradoxes of the type of the Kochen-Specker Theorem, which can then be easily rephrased into proposals for new no hidden variable experiments of the type of the ``Bell Theorem without inequalities\\\'\\\'.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/222800739nas a2200109 4500008004100000245008000041210007100121260001300192520036600205100002200571856003600593 2005 en d00aExplicit Wei–Norman formulae for matrix Lie groups via Putzer\\\'s method0 aExplicit Wei–Norman formulae for matrix Lie groups via Putzers m bElsevier3 aThe Wei–Norman formula locally relates the Magnus solution of a system of linear time-varying ODEs with the solution expressed in terms of products of exponentials by means of a set of nonlinear differential equations in the parameters of the two types of solutions. A closed form expression of such formula is proposed based on the use of Putzer\\\'s method.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/453800697nas a2200097 4500008004300000245005500043210005500098520038800153100002200541856003600563 2004 en_Ud 00aCoherent control of open quantum dynamical systems0 aCoherent control of open quantum dynamical systems3 aA systematic analysis of the behavior of the quantum Markovian master equation driven by coherent control fields is proposed. Its irreversible character is formalized using control-theoretic notions and the sets of states that can be reached via cohere nt controls are described. The analysis suggests to which extent (and how) it is possible to counteract the effect of dissipation.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/222701711nas a2200109 4500008004300000245014800043210006900191260001700260520126600277100002201543856003601565 2004 en_Ud 00aReduction by group symmetry of second order variational problems on a semidirect product of Lie groups with positive definite Riemannian metric0 aReduction by group symmetry of second order variational problems bEDP Sciences3 aFor a Riemannian structure on a semidirect product of Lie groups, the variational problems can be reduced using the group symmetry. Choosing the Levi-Civita connection of a positive definite metric tensor, instead of any of the canonical connections for the Lie group, simplifies the reduction of the variations but complicates the expression for the Lie algebra valued covariant derivatives. The origin of the discrepancy is in the semidirect product structure, which implies that the Riemannian exponential map and the Lie group exponential map do not coincide. The consequence is that the reduced equations look more complicated than the original ones. The main scope of this paper is to treat the reduction of second order variational problems (corresponding to geometric splines) on such semidirect products of Lie groups. Due to the semidirect structure, a number of extra terms appears in the reduction, terms that are calculated explicitely. The result is used to compute the necessary conditions of an optimal control problem for a simple mechanical control system having invariant Lagrangian equal to the kinetic energy corresponding to the metric tensor. As an example, the case of a rigid body on the Special Euclidean group is considered in detail.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/352101168nas a2200097 4500008004300000245006600043210006600109520083700175100002201012856003601034 2004 en_Ud 00aRepresenting multiqubit unitary evolutions via Stokes tensors0 aRepresenting multiqubit unitary evolutions via Stokes tensors3 aFor the Stokes tensor parametrization of a multiqubit density operator, we provide an explicit formulation of the corresponding unitary dynamics at the infinitesimal level. The main advantage of this formalism (clearly reminiscent of the ideas of ``coherences\\\'\\\' and ``coupling Hamiltonians\\\'\\\' of spin systems) is that the pattern of correlation between qubits and the pattern of infinitesimal correlation are highlighted simultaneously and can be used constructively for qubit manipulation. For example, it allows to compute explicitly a Rodrigues\\\' formula for the one-parameter orbits of nonlocal Hamiltonians. The result is easily generalizable to orbits of Cartan subalgebras and allows to express the Cartan decomposition of unitary propagators as a linear action directly in terms of the infinitesimal generators.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/230701375nas a2200109 4500008004300000245010700043210006900150260003000219520095800249100002201207856003601229 2004 en_Ud 00aTensor of coherences parametrization of multiqubit density operators for entanglement characterization0 aTensor of coherences parametrization of multiqubit density opera bAmerican Physical Society3 aFor multiqubit densities, the tensor of coherences (or Stokes tensor) is a real parameterization obtained by the juxtaposition of the affine Bloch vectors of each qubit. While it maintains the tensorial structure of the underlying space, it highlights the pattern of correlations, both classical and quantum, between the subsystems and, due to the affine parameterization, it contains in its components all reduced densities of all orders. The main purpose of our use of this formalism is to deal with entanglement. For example, the detection of bipartite entanglement is straightforward, as it is the synthesis of densities having positive partial transposes between desired qubits. In addition, finding explicit mixtures for families of separable states becomes a feasible issue for few qubit symmetric densities (we compute it for Werner states) and, more important, it provides some insight on the possible origin of entanglement for such densities.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/284500974nas a2200109 4500008004300000245008900043210006900132260003400201520057100235100002200806856003600828 2003 en_Ud 00aControllability properties for finite dimensional quantum Markovian master equations0 aControllability properties for finite dimensional quantum Markov bAmerican Institute of Physics3 aVarious notions from geometric control theory are used to characterize the behavior of the Markovian master equation for N-level quantum mechanical systems driven by unitary control and to describe the structure of the sets of reachable states. It is shown that the system can be accessible but neither small-time controllable nor controllable in finite time. In particular, if the generators of quantum dynamical semigroups are unital, then the reachable sets admit easy characterizations as they monotonically grow in time. The two level case is treated in detail.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/290901411nas a2200109 4500008004300000245012000043210006900163260001000232520100100242100002201243856003601265 2003 en_Ud 00aGeometric motion control for a kinematically redundant robotic chain: application to a holonomic mobile manipulator0 aGeometric motion control for a kinematically redundant robotic c bWiley3 aFor kinematically redundant robotic manipulators, the extra degrees of freedom available allows freedom in the generation of the trajectories of the end-effector. In this paper, for this scope, we use techniques for motion control of rigid bodies on Riemannian manifolds (and Lie groups in particular) to design workspace control algorithms for the end-effector of the robotic chain and then to pull them back to joint space, all respecting the different geometric structures of the two underlying model spaces. The trajectory planner makes use of geometric splines. Examples of the different kinds of curves that are obtained via the De Casteljau algorithm in correspondence of different metric structures in SE(3) are reported. The feedback module, instead, consists of a Lyapunov based PD controller defined from a suitable notion of error distance on the Lie group. The motivating application of our work is a holonomic mobile manipulator for which simulation results are described in detail.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/301901197nas a2200121 4500008004300000245012700043210006900170260001300239520074500252100002200997700002001019856003601039 2003 en_Ud 00aMotion on submanifolds of noninvariant holonomic constraints for a kinematic control system evolving on a matrix Lie group0 aMotion on submanifolds of noninvariant holonomic constraints for bElsevier3 aFor a control system on a matrix Lie group with one or more configuration constraints that are not left/right invariant, finding the combinations of (kinematic) control inputs satisfying the motion constraints is not a trivial problem. Two methods, one coordinate-dependent and the other coordinate-free are suggested. The first is based on the Wei-Norman formula; the second on the calculation of the annihilator of the coadjoint action of the constraint one-form at each point of the group manifold. The results are applied to a control system on SE(3) with a holonomic inertial constraint involving the noncommutative part in a nontrivial way. The difference in terms of compactness of the result between the two methods is considerable.1 aAltafini, Claudio1 aFrezza, Ruggero uhttp://hdl.handle.net/1963/301800793nas a2200109 4500008004300000245010200043210006900145260001300214520039800227100002200625856003600647 2003 en_Ud 00aParameter differentiation and quantum state decomposition for time varying Schrödinger equations0 aParameter differentiation and quantum state decomposition for ti bElsevier3 aFor the unitary operator, solution of the Schroedinger equation corresponding to a time-varying Hamiltonian, the relation between the Magnus and the product of exponentials expansions can be expressed in terms of a system of first order differential equations in the parameters of the two expansions. A method is proposed to compute such differential equations explicitly and in a closed form.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/301700371nas a2200097 4500008004100000245008700041210006900128260001800197100002200215856003600237 2002 en d00aControllability of quantum mechanical systems by root space decomposition of su(N)0 aControllability of quantum mechanical systems by root space deco bSISSA Library1 aAltafini, Claudio uhttp://hdl.handle.net/1963/161300768nas a2200109 4500008004300000245007400043210006900117260000900186520040500195100002200600856003600622 2002 en_Ud 00aFollowing a path of varying curvature as an output regulation problem0 aFollowing a path of varying curvature as an output regulation pr bIEEE3 aGiven a path of nonconstant curvature, local asymptotic stability can be proven for the general n trailer whenever the curvature can be considered as the output of an exogenous dynamical system. The controllers that provide convergence to zero of the tracking error chosen for the path-following problem are composed of a prefeedback that input-output linearizes the system, plus a linear controller.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/314300403nas a2200097 4500008004100000245011900041210006900160260001800229100002200247856003600269 2002 en d00aOn the generation of sequential unitary gates from continuous time Schrodinger equations driven by external fields0 ageneration of sequential unitary gates from continuous time Schr bSISSA Library1 aAltafini, Claudio uhttp://hdl.handle.net/1963/161401047nas a2200109 4500008004300000245006200043210005800105260001300163520070300176100002200879856003600901 2002 en_Ud 00aThe reachable set of a linear endogenous switching system0 areachable set of a linear endogenous switching system bElsevier3 aIn this work, switching systems are named endogenous when their switching pattern is controllable. Linear endogenous switching systems can be considered as a particular class of bilinear control systems. The key idea is that both types of systems are equivalent to polysystems, i.e. to systems whose flow is piecewise smooth. The reachable set of a linear endogenous switching system can be studied consequently. The main result is that, in general, it has the structure of a semigroup, even when the Lie algebra rank condition is satisfied since the logic inputs cannot reverse the direction of the flow. The adaptation of existing controllability criteria for bilinear systems is straightforward.1 aAltafini, Claudio uhttp://hdl.handle.net/1963/3142