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3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification., Comment: Added two references

We discuss a simple and powerful approach for the ab initio identification of cis-regulatory motifs involved in transcriptional regulation. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites., Comment: 22 pages, 2 figures. Supplementary material available from the authors

BACKGROUND: Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated gene. The computational identification of such motifs is made easier by the fact that they often appear several times in the upstream region of the regulated genes, so that the number of occurrences of relevant motifs is often significantly larger than expected by pure chance. RESULTS: To exploit this fact, we construct sets of genes characterized by the statistical overrepresentation of a certain motif in their upstream regions. Then we study the functional characterization of these sets by analyzing their annotation to Gene Ontology terms. For the sets showing a statistically significant specific functional characterization, we conjecture that the upstream motif characterizing the set is a binding site for a transcription factor involved in the regulation of the genes in the set. CONCLUSIONS: The method we propose is able to identify many known binding sites in S. cerevisiae and new candidate targets of regulation by known transcription factors. Its application to less well studied organisms is likely to be valuable in the exploration of their regulatory interaction network., Comment: 19 pages, 1 figure. Published version with several improvements. Supplementary material available from the authors

Gene regulation in Eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of Eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: if this level is significantly higher or lower than the average taken over the whole genome, then the overrepresented motif shared by the genes in the set is likely to play a role in their regulation. We illustrate the method by applying it to the genome of {\it S. cerevisiae}, for which many datasets of microarray experiments are publicly available. Several known binding motifs are correctly recognized by our algorithm, and a new candidate is suggested for experimental verification., Comment: 7 pages, 2 figures

We study spatial networks constructed by randomly placing nodes on a manifold and joining two nodes with an edge whenever their distance is less than a certain cutoff. We derive the general expression for the connectivity distribution of such networks as a functional of the distribution of the nodes. We show that for regular spatial densities, the corresponding spatial network has a connectivity distribution decreasing faster than an exponential. In contrast, we also show that scale-free networks with a power law decreasing connectivity distribution are obtained when a certain information measure of the node distribution (integral of higher powers of the distribution) diverges. We illustrate our results on a simple example for which we present simulation results. Finally, we speculate on the role played by the limiting case P(k)=1/k which appears empirically to be relevant to spatial networks of biological origin such as the ones constructed from gene expression data., Comment: 6 pages, 1 figure

We discuss the spectrum of screening masses in a pure gauge theory near the deconfinement temperature from the point of view of the dimensionally reduced model describing the spontaneous breaking of the center symmetry. Universality arguments can be used to predict the values of the mass ratios in the scaling region of the deconfined phase when the transition is of second order. One such prediction is that the scalar sector of the screening spectrum in SU(2) pure gauge theory contains a bound state of the fundamental excitation, corresponding through universality to the bound state found in the 3D Ising model and phi^4 theory in the broken symmetry phase. A Monte Carlo evaluation of the screening masses in the gauge theory confirms the validity of the prediction. We briefly discuss the possibility of using similar arguments for first order deconfinement transitions, and in particular for the physically relevant case of SU(3)., Comment: 12 pages, 3 figures. Some changes in the discussion, added references, results unchanged. Version to appear in Phys. Rev. D

We study the role of percolating clusters of center vortices in configurations of an Ising gauge theory in 3D. It is known that low energy features of gauge theories can be described in terms of an ``effective string picture'', and that confinement properties are associated with topologically non-trivial configurations. We focus our attention upon percolating clusters of center vortices, and present numerical evidence for the fact that these objects play a preminent role in confinement phenomenon, since their removal sweeps off confinement altogether. Moreover, numerical simulations show that the string fluctuations, and in particular the Luescher term, are completely encoded in the percolating cluster., Comment: Lattice2002(topology); added reference

We compare the predictions of the effective string description of confinement in finite temperature gauge theories to high precision Monte Carlo data for the three-dimensional Z(2) gauge theory. We show that string interaction effects become more relevant as the temperature is increased towards the deconfinement one, and are well modeled by a Nambu-Goto string action., Comment: Lattice2002(nonzerot)

We study the spectrum of screening masses in the deconfined phase of (3+1)D SU(2) pure gauge theory near criticality and compare it with the spectrum of bound states in the broken symmetry phase of the 3D Ising model, which is related to the gauge theory by universality., Comment: 3 pages, uses espcrc2.sty, Lattice2002(nonzerot)

We construct a gene network based on expression data from DNA microarray experiments, by establishing a link between two genes whenever the Pearson's correlation coefficient between their expression profiles is higher than a certain cutoff. The resulting connectivity distribution is compatible with a power-law decay with exponent ~1, corrected by an exponential cutoff at large connectivity. The biological relevance of such network is demonstrated by showing that there is a strong statistical correlation between high connectivity number and lethality: in close analogy to what happens for protein interaction networks, essential genes are strongly overerpresented among the hubs of the network, that is the genes connected to many other genes.

The confining mechanisms of 't Hooft and Mandelstam have a simple microscopic realization in 3D Z2 gauge theory: the center vortex and the magnetic monopole condensation are associated, in the set of configurations contributing to the confining phase, to the presence of two kinds of infinite clusters. These generate the area law of the large Wilson loops and the universal finite size effects produced by the quantum fluctuations of the bosonic string describing the infrared behavior of the flux tube., Comment: 8 pages, 4 eps figures. Contributed to NATO Advanced Research Workshop on Confinement, Topology, and other Nonperturbative Aspects of QCD, Stara Lesna, Slovakia, 21-27 Jan 2002

We study the role of large clusters of center vortices in producing confinement in 3D Z(2) gauge theory. First, we modify each configuration of a Monte Carlo-generated ensemble in the confined phase by removing the largest cluster of center vortices, and show that the ensemble thus obtained does not confine. Conversely, we show that removing all of the small clusters of center vortices and leaving the largest one only, confinement is preserved, albeit with a string tension significantly smaller than the original one. Remarkably, also the string corrections due to the quantum fluctuations of the confining flux tube are preserved by this transformation., Comment: 8 pages,5 figures

Gene regulation in eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: If this level is significantly higher or lower than the average taken over the whole genome, then the overerpresented motif shared by the genes in the set is likely to play a role in their regulation. The method was tested by applying it to the genome of Saccharomyces cerevisiae, using the publicly available results of a DNA microarray experiment, in which expression levels for virtually all the genes were measured during the diauxic shift from fermentation to respiration. Several known motifs were correctly identified, and a new candidate regulatory sequence was determined., Comment: Published version available from http://www.biomedcentral.com/1471-2105/3/7

Branched n-coverings of Riemann surfaces are described by a 2d lattice gauge theory of the symmetric group S(n) defined on a cell discretization of the surface. We study the theory in the large-n limit, and we find a rich phase diagram with first and second order transition lines. The various phases are characterized by different connectivity properties of the covering surface. We point out some interesting connections with the theory of random walks on group manifolds and with random graph theory., Comment: Talk presented at the "Light-cone physics: particles and strings", Trento, Italy, September 2001

We discuss two new approaches to extract relevant biological information on the Transcription Factors (and in particular to identify their binding sequences) from the statistical distribution of oligonucleotides in the upstream region of the genes. Both the methods are based on the notion of a ``regulatory network'' responsible for the various expression patterns of the genes. In particular we concentrate on families of coregulated genes and look for the simultaneous presence in the upstream regions of these genes of the same set of transcription factor binding sites. We discuss two instances which well exemplify the features of the two methods: the coregulation of glycolysis in Drosophila melanogaster and the diauxic shift in Saccharomyces cerevisiae., Comment: 12 pages. Contribution to the proceedings of the International Workshop ``Modelling Bio-medical signals'', Bari, September 2001

We study the two-dimensional gauge theory of the symmetric group S_n describing the statistics of branched n-coverings of Riemann surfaces. We consider the theory defined on the disk and on the sphere in the large-n limit. A non trivial phase structure emerges, with various phases corresponding to different connectivity properties of the covering surface. We show that any gauge theory on a two-dimensional surface of genus zero is equivalent to a random walk on the gauge group manifold: in the case of S_n, one of the phase transitions we find can be interpreted as a cutoff phenomenon in the corresponding random walk. A connection with the theory of phase transitions in random graphs is also pointed out. Finally we discuss how our results may be related to the known phase transitions in Yang-Mills theory. We discover that a cutoff transition occurs also in two dimensional Yang-Mills theory on a sphere, in a large N limit where the coupling constant is scaled with N with an extra log N compared to the standard 't Hooft scaling., Comment: 27 pages, 3 figures. New results on the connection with Yang-Mills theories

We study the spectrum of bound states of the three dimensional Ising model in the (h,beta) plane near the critical point. We show the existence of an unbinding line, defined as the boundary of the region where bound states exist. Numerical evidence suggests that this line coincides with the beta=beta_c axis. When the 3D Ising model is considered as an effective description of hot QCD at finite density, we conjecture the correspondence between the unbinding line and the line that separates the quark-gluon plasma phase from the superconducting phase. The bound states of the Ising model are conjectured to correspond to the diquarks of the latter phase of QCD., Comment: Lattice2001(hightemp)

A new method is proposed for determining the critical indices of the deconfinement transition in gauge theories, based on the finite-size scaling analysis of simple lattice operators, such as the plaquette. A precise determination of the critical index $\nu$, in agreement with the prediction of the Svetitsky-Yaffe conjecture, is obtained for SU(3) gauge theory in (2+1)-dimension. Preliminary results for SU(2) in (3+1)-dimension are also given., Comment: poster at Lattice2001(hightemp), 3 pages, 2 figures, uses espcrc2.sty

We construct the lattice gauge theory of the group G_N, the semidirect product of the permutation group S_N with U(1)^N, on an arbitrary Riemann surface. This theory describes the branched coverings of a two-dimensional target surface by strings carrying a U(1) gauge field on the world sheet. These are the non-supersymmetric Matrix Strings that arise in the unitary gauge quantization of a generalized two-dimensional Yang-Mills theory. By classifying the irreducible representations of G_N, we give the most general formulation of the lattice gauge theory of G_N, which includes arbitrary branching points on the world sheet and describes the splitting and joining of strings., Comment: LaTeX2e, 25 pages, 4 figures

We study the spectrum of massive excitations in three-dimensional models belonging to the Ising universality class. By solving the Bethe-Salpeter equation for 3D $\phi^4$ theory in the broken symmetry phase we show that recently found non-perturbative states can be interpreted as bound states of the fundamental excitation. We show that duality predicts an exact correspondence between the spectra of the Ising model in the broken symmetry phase and of the Z(2) gauge theory in the confining phase. The interpretation of the glueball states of the gauge theory as bound states of the dual spin system allows us to explain the qualitative features of the glueball spectrum, in particular, its peculiar angular momentum dependence., Comment: 24 pages, 6 figures

We introduce a new method for determining the critical indices of the deconfinement transition in gauge theories. The method is based on the finite size scaling behavior of the expectation value of simple lattice operators, such as the plaquette. We test the method for the case of SU(3) pure gauge theory in (2+1) dimensions and obtain a precise determination of the critical index $\nu$, in agreement with the prediction of the Svetitsky-Yaffe conjecture., Comment: 6 pages. Several comments and one reference added, results unchanged

We discuss the spectrum of the three dimensional phi^4 theory in the broken symmetry phase. In this phase the effective potential between the elementary quanta of the model is attractive and bound states of two or more of them may exist. We give theoretical and numerical evidence for the existence of these bound states. Looking in particular at the Ising model realization of the phi^4 theory we show, by using duality, that these bound states are in one-to-one correspondence with the glueball states of the gauge Ising model. We discuss some interesting consequences of this identification., Comment: 4 pages, 3 figures. Numerical value of the preexponential factor in the binding energy corrected, all other results and conclusions unchanged

We consider two-dimensional Yang-Mills theories on arbitrary Riemann surfaces. We introduce a generalized Yang-Mills action, which coincides with the ordinary one on flat surfaces but differs from it in its coupling to two-dimensional gravity. The quantization of this theory in the unitary gauge can be consistently performed taking into account all the topological sectors arising from the gauge-fixing procedure. The resulting theory is naturally interpreted as a Matrix String Theory, that is as a theory of covering maps from a two-dimensional world-sheet to the target Riemann surface., Comment: LaTeX, 10 pages, uses espcrc2.sty. Presented by A. D'adda at the Third Meeting on Constrained Dynamics and Quantum Gravity, Villasimius (Sardinia, Italy) September 13-17, 1999; to appear in the proceedings

We quantize pure 2d Yang-Mills theory on an arbitrary Riemann surface in the gauge where the field strength is diagonal. Twisted sectors originate, as in Matrix string theory, from permutations of the eigenvalues around homotopically non-trivial loops. These sectors, that must be discarded in the usual quantization due to divergences occurring when two eigenvalues coincide, can be consistently kept if one modifies the action by introducing a coupling of the field strength to the space-time curvature. This leads to a generalized Yang-Mills theory whose action reduces to the usual one in the limit of zero curvature. After integrating over the non-diagonal components of the gauge fields, the theory becomes a free string theory (sum over unbranched coverings) with a U(1) gauge theory on the world-sheet. This is shown to be equivalent to a lattice theory with a gauge group which is the semi-direct product of S_N and U(1)^N. By using well known results on the statistics of coverings, the partition function on arbitrary Riemann surfaces and the kernel functions on surfaces with boundaries are calculated. Extensions to include branch points and non-abelian groups on the world-sheet are briefly commented upon., Comment: Latex2e, 29 pages, 2 .eps figures

The confining string in presence of dynamical quarks can behave in different ways, depending on the quark masses and on the number N_f N_c of charge species. For light masses and large N_f N_c the creation of quark pairs produces microscopic holes in the world- sheet swept by the string; as a consequence string breaking is invisible in the Wilson loop, while is manifest in operators composed of disjoint sources, as observed in many numerical experiments. Similar arguments apply also to the adjoint string breaking. For larger quark masses it is possible that the string world-sheet undergoes a transition to a tearing phase, characterized by macroscopic holes, which manifest themselves through a visible string breaking effect also in the Wilson loop, as observed in 2+1 D SU(2) gauge theory with two flavors., Comment: LATTICE99(confine)- 3 pages, 5 eps figures

We study the spectrum of massive excitations of the three-dimensional phi^4 and Ising models, in the broken-symmetry phase. Using a variational method, we show that the spectrum contains all the 0+ states that one expects from duality with the glueball spectrum of the Z(2) gauge model. From the point of view of continuum phi^4 theory, we show that at least one of the states we find has a non-perturbative origin., Comment: LATTICE99(spin) - 3 pages, 2 encapsulated postscript figures

We point out that the world sheet swept by the confining string in presence of dynamical quarks can belong to two different phases, depending on the number of charge species and the quark masses. When it lies in the normal phase (as opposed to the tearing one) the string breaking is invisible in the Wilson loop, while is manifest in operators composed of disjoint sources, as observed in many numerical experiments. We work out an explicit formula for the correlator of Polyakov loops at finite temperature, which is then compared with recent lattice data, both in the quenched case and in presence of dynamical quarks. The analysis in the quenched case shows that the free bosonic string model describes accurately the data for distances larger than ~ 0.75 fm. In the unquenched case we derive predictions on the dependence of the static potential on the temperature which are compatible with the lattice data., Comment: 15 pages, LaTeX with 4 eps figures (included)

We show that the spectrum of the three dimensional phi^4 theory in the broken symmetry phase contains non-perturbative states. We determine the spectrum using a new variational technique based on the introduction of operators corresponding to different length scales. The presence of non-perturbative states accounts for the discrepancy between Monte Carlo and perturbative results for the universal ratio xi/xi_2nd. We introduce and study some universal amplitude ratios related to the overlap of the spin operator with the states of the spectrum. The analysis is performed for the phi^4 theory regularized on a lattice and for the Ising model. This is a nice verification of the fact that universality reaches far beyond critical exponents. Finally, we show that the spectrum of the model, including non-perturbative states, accurately matches the glueball spectrum in the Z(2) gauge model, which is related to the Ising model through a duality transformation., Comment: 43 pages, LaTeX with 9 eps figures included, uses axodraw.sty

Quantization of two-dimensional Yang-Mills theory on a torus in the gauge where the field strength is diagonal leads to twisted sectors that are completely analogous to the ones that originate long string states in Matrix String Theory. If these sectors are taken into account the partition function is different from the standard one found in the literature and the invariance of the theory under modular transformations of the torus appears to hold in a stronger sense. The twisted sectors are in one-to-one correspondence with the coverings of the torus without branch points, so they define by themselves a string theory. A possible duality between this string theory and the Gross-Taylor string is discussed, and the problems that one encounters in generalizing this approach to interacting strings are pointed out. This talk is based on a previous paper by the same authors, but it contains some new results and a better interpretation of the results already obtained., Comment: 11 pages, LaTeX, 2 figures included with epsf. Talk presented at the 2nd Conference on Quantum aspects of Gauge Theories, Supersymmetry and Unification, Corfu, Greece, 21-26 September 1996