This work investigates the emergence of oscillations in one of the simplest cellular signaling networks exhibiting oscillations, namely, the dual-site phosphorylation and dephosphorylation network (futile cycle), in which the mechanism for phosphorylation is processive while the one for dephosphorylation is distributive (or vice-versa). The fact that this network yields oscillations was shown recently by Suwanmajo and Krishnan. Our results, which significantly extend their analyses, are as follows. First, in the three-dimensional space of total amounts, the border between systems with a stable versus unstable steady state is a surface defined by the vanishing of a single Hurwitz determinant. Second, this surface consists generically of simple Hopf bifurcations. Next, simulations suggest that when the steady state is unstable, oscillations are the norm. Finally, the emergence of oscillations via a Hopf bifurcation is enabled by the catalytic and association constants of the distributive part of the mechanism: if these rate constants satisfy two inequalities, then the system generically admits a Hopf bifurcation. Our proofs are enabled by the Routh-Hurwitz criterion, a Hopf-bifurcation criterion due to Yang, and a monomial parametrization of steady states.
Our work joins a growing number of works that harness steady-state parametrizations. Such results include criteria for when such parametrizations exist @cite_19 @cite_37 and methods for using them to determine whether a network is multistationary @cite_20 @cite_23 @cite_27 @cite_2 . Going further, steady-state parametrizations can also be used to find a witness to multistationarity or even the precise parameter regions that yield multistationarity @cite_13 @cite_39 . In this work, we use a steady-state parametrization in a novel way: to study oscillations via Hopf bifurcations. (Our approach is similar in spirit to using Clarke's convex parameters together with a Hopf-bifurcation criterion @cite_31 @cite_15 @cite_22 @cite_10 ).
@cite_37 @cite_22 @cite_15 @cite_10 @cite_39 @cite_19 @cite_27 @cite_23 @cite_2 @cite_31 @cite_13 @cite_20
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We study the approximability of multiway partitioning problems, examples of which include Multiway Cut, Node-weighted Multiway Cut, and Hypergraph Multiway Cut. We investigate these problems from the point of view of two possible generalizations: as Min-CSPs, and as Submodular Multiway Partition problems. These two generalizations lead to two natural relaxations that we call respectively the Local Distribution LP, and the Lovasz relaxation. The Local Distribution LP is generally stronger than the Lovasz relaxation, but applicable only to Min-CSP with predicates of constant size. The relaxations coincide in some cases such as Multiway Cut where they are both equivalent to the CKR relaxation. We show that the Lovasz relaxation gives a (2--2 k)-approximation for Submodular Multiway Partition with k terminals, improving a recent 2-approximation [2]. We prove that this factor is optimal in two senses: (1) A (2--2 k -- e)-approximation for Submodular Multiway Partition with k terminals would require exponentially many value queries (in the oracle model), or imply NP = RP (for certain explicit submodular functions). (2) For Hypergraph Multiway Cut and Node-weighted Multiway Cut with k terminals, both special cases of Submodular Multiway Partition, we prove that a (2--2 k -- e)-approximation is NP-hard, assuming the Unique Games Conjecture. Both our hardness results are more general: (1) We show that the notion of symmetry gap, previously used for submodular maximization problems [19, 6], also implies hardness results for submodular minimization problems. (2) Assuming the Unique Games Conjecture, we show that the Local Distribution LP gives an optimal approximation for every Min-CSP that includes the Not-Equal predicate. Finally, we connect the two hardness techniques by proving that the integrality gap of the Local Distribution LP coincides with the symmetry gap of the multilinear relaxation (for a related instance). This shows that the appearance of the same hardness threshold for a Min-CSP and the related submodular minimization problem is not a coincidence. Bifurcation theory is one of the most widely used approaches for analysis of dynamical behaviour of chemical and biochemical reaction networks. Some of the interesting qualitative behaviour that are analyzed are oscillations and bistability (a situation where a system has at least two coexisting stable equilibria). Both phenomena have been identified as central features of many biological and biochemical systems. This paper, using the theory of stoichiometric network analysis (SNA) and notions from algebraic geometry, presents sufficient conditions for a reaction network to display bifurcations associated with these phenomena. The advantage of these conditions is that they impose fewer algebraic conditions on model parameters than conditions associated with standard bifurcation theorems. To derive the new conditions, a coordinate transformation will be made that will guarantee the existence of branches of positive equilibria in the system. This is particularly useful in mathematical biology, where only positive variable values are considered to be meaningful. The first part of the paper will be an extended introduction to SNA and algebraic geometry-related methods which are used in the coordinate transformation and set up of the theorems. In the second part of the paper we will focus on the derivation of bifurcation conditions using SNA and algebraic geometry. Conditions will be derived for three bifurcations: the saddle-node bifurcation, a simple branching point, both linked to bistability, and a simple Hopf bifurcation. The latter is linked to oscillatory behaviour. The conditions derived are sufficient and they extend earlier results from stoichiometric network analysis as can be found in (Aguda and Clarke in J Chem Phys 87:3461-3470, 1987; Clarke and Jiang in J Chem Phys 99:4464-4476, 1993; in J Symb Comput 40:1361-1382, 2005). In these papers some necessary conditions for two of these bifurcations were given. A set of examples will illustrate that algebraic conditions arising from given sufficient bifurcation conditions are not more difficult to interpret nor harder to calculate than those arising from necessary bifurcation conditions. Hence an increasing amount of information is gained at no extra computational cost. The theory can also be used in a second step for a systematic bifurcation analysis of larger reaction networks. Abstract We consider boundary value problems for semilinear hyperbolic systems of the type ∂ t u j + a j ( x , λ ) ∂ x u j + b j ( x , λ , u ) = 0 , x ∈ ( 0 , 1 ) , j = 1 , … , n , with smooth coefficient functions a j and b j such that b j ( x , λ , 0 ) = 0 for all x ∈ [ 0 , 1 ] , λ ∈ R , and j = 1 , … , n . We state conditions for Hopf bifurcation, i.e., for existence, local uniqueness (up to phase shifts), smoothness and smooth dependence on λ of time-periodic solutions bifurcating from the zero stationary solution. Furthermore, we derive a formula which determines the bifurcation direction. The proof is done by means of a Liapunov–Schmidt reduction procedure. For this purpose, Fredholm properties of the linearized system and implicit function theorem techniques are used. Mulmuley [Mul12a] recently gave an explicit version of Noether’s Normalization lemma for ring of invariants of matrices under simultaneous conjugation, under the conjecture that there are deterministic black-box algorithms for polynomial identity testing (PIT). He argued that this gives evidence that constructing such algorithms for PIT is beyond current techniques. In this work, we show this is not the case. That is, we improve Mulmuley’s reduction and correspondingly weaken the conjecture regarding PIT needed to give explicit Noether Normalization. We then observe that the weaker conjecture has recently been nearly settled by the authors ([FS12]), who gave quasipolynomial size hitting sets for the class of read-once oblivious algebraic branching programs (ROABPs). This gives the desired explicit Noether Normalization unconditionally, up to quasipolynomial factors. As a consequence of our proof we give a deterministic parallel polynomial-time algorithm for deciding if two matrix tuples have intersecting orbit closures, under simultaneous conjugation. We also study the strength of conjectures that Mulmuley requires to obtain similar results as ours. We prove that his conjectures are stronger, in the sense that the computational model he needs PIT algorithms for is equivalent to the well-known algebraic branching program (ABP) model, which is provably stronger than the ROABP model. Finally, we consider the depth-3 diagonal circuit model as defined by Saxena [Sax08], as PIT algorithms for this model also have implications in Mulmuley’s work. Previous work (such as [ASS12] and [FS12]) have given quasipolynomial size hitting sets for this model. In this work, we give a much simpler construction of such hitting sets, using techniques of Shpilka and Volkovich [SV09].