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A singular limit for an age structured mutation problem

  • Received: 31 October 2015 Accepted: 10 March 2016 Published: 01 February 2017
  • MSC : Primary: 34E15, 92D25; Secondary: 34E13

  • The spread of a particular trait in a cell population often is modelled by an appropriate system of ordinary differential equations describing how the sizes of subpopulations of the cells with the same genome change in time. On the other hand, it is recognized that cells have their own vital dynamics and mutations, leading to changes in their genome, mostly occurring during the cell division at the end of its life cycle. In this context, the process is described by a system of McKendrick type equations which resembles a network transport problem. In this paper we show that, under an appropriate scaling of the latter, these two descriptions are asymptotically equivalent.

    Citation: Jacek Banasiak, Aleksandra Falkiewicz. A singular limit for an age structured mutation problem[J]. Mathematical Biosciences and Engineering, 2017, 14(1): 17-30. doi: 10.3934/mbe.2017002

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  • The spread of a particular trait in a cell population often is modelled by an appropriate system of ordinary differential equations describing how the sizes of subpopulations of the cells with the same genome change in time. On the other hand, it is recognized that cells have their own vital dynamics and mutations, leading to changes in their genome, mostly occurring during the cell division at the end of its life cycle. In this context, the process is described by a system of McKendrick type equations which resembles a network transport problem. In this paper we show that, under an appropriate scaling of the latter, these two descriptions are asymptotically equivalent.


    1. Introduction

    An important problem related to mutations is to understand how a particular trait spreads in a population. One of the simplest ways to model this is to describe the change in the sizes of subpopulations having this trait. It can be done by the standard balancing argument: the rate of change of the number of, say, cells with a particular genome γ is equal to the rate of recruitment of cells with other genomes that change, due to mutations, to γ, minus the rate at which the mutations cause the cells with genome γ to move to subpopulations with another genome. This balance equation typically is supplemented by terms describing the death and proliferation of the cells. Models of this type were extensively studied, see for instance [8,12,15,16,22], either in the context of the development of drug resistance in cancer cells, or in describing the micro-satellite repeats. In the former, a population of cells was divided into smaller subpopulations according to the number of the drug resistant gene, while in the latter the feature of interest was the number of the micro-satellite repeats. In both cases the authors only allowed for changes between neighbouring populations, which resulted in the birth-and-death system with proliferation,

    u0=a0u0+d1u1,u1=a1u1+d2u2,un=anun+bn1un1+dn+1un+1,n2, (1)

    where un is the number of cells belonging to the subpopulation n, n=0,1,2 (e.g. having n drug-resistant genes), dn+1,bn1 are the rates of recruitment from the populations n+1 and n1 into the population n and an is the net growth rate of the population n which incorporates birth, death and loss to other populations of cells of type n. We note that the particular form of (1), in which the first equation is decoupled from the rest, is due to the assumption adopted in op.cit. that any object in the state 0 can generate only objects in the same state. This assumption, however, is of no significance in our considerations.

    It is clear that, in principle, jumps between arbitrary populations can occur and thus there is no need to restrict our attention to tridiagonal matrices. We can consider a general model

    u=Lu, (2)

    where u=(ui)iN and L=(lij)i,jN, NN may be infinite and L is a positive off-diagonal matrix, where the off-diagonal term lij is the rate at which the cells are recruited into the population i, characterized by a particular genotype, from the population j. The diagonal entries represent the loss rates from corresponding classes.

    At the same time it is recognized that the cells have their own vital dynamics that should be taken into account if a more detailed model of the evolution of the whole population is to be built. Also, the mutations can be divided into various groups. Here, we distinguish two types of mutations: those that are due to the replication errors and occur when the cell divides, and others, due to external factors (mutagenes), that may happen at any moment of the cell's life cycle. This results in a model of the form

    tu(x,t)+Vxu(x,t)=Mu(x,t)+Ru(x,t),x(0,1),t0,u(x,0)=˚u(x),u(0,t)=Ku(1,t), (3)

    where we consider a population of cells described by their density uj(x) in each class jN, and where x is a parameter describing the maturity of the cell, typically its age or size. In general, cells in each class can divide at a different age (or size), say τj, so that we normalize the age of division to 1 by introducing the maturation velocities V=diag(vi)iN, where vi=1/τi. Cells are born at x=0 and divide at x=1 producing, due to mutations during mitosis, daughter cells of an arbitrary class, the distribution of which is governed by a nonnegative matrix K=(kij)i,jN. Though typical mitosis produces two daughter particles, this is not always the case. For instance, cancer cells can produce up to five daughter cells, [23], so that we shall not place any further restrictions on K. Further, M=diag(μj)jN gives the death rates due to external causes and R=(rij)i,jN describes redistribution of cells caused by mutations due to external factors (mutagenes). Finally, the nonnegative vector ˚u describes the initial population. A classical example of this type is the discrete Lebowitz-Rubinow-Rotenberg model in which the cells' populations are distinguished precisely by the maturation velocities, [21].

    The main objective of this paper is to determine under what conditions can solutions to (3) be approximated by the solutions of (2). There could be several ways to approach this problem and the answer may be not unique. Our approach is to assume that the maturation velocities are very large or, in other words, the cells divide many times in the reference unit of time, while the deaths and mutations due to external causes remain at fixed, independent of the maturation velocity, levels. To balance the fact that there is a large number of cell divisions in the unit time, we assume that the daughter cells have a tendency to be of the same genotype as the mother (see e.g. [18,p. 19]), which is represented by splitting the boundary operator as K=I+ϵB, ϵ1. Thus, we will consider the singularly perturbed problem

    tuϵ(x,t)+ϵ1Vxuϵ(x,t)=Muϵ(x,t)+Ruϵ(x,t),x(0,1),t0,uϵ(x,0)=˚u(x),uϵ(0,t)=(I+ϵB)uϵ(1,t), (4)

    where I is the identity matrix. By l1N we denote RN equipped with the l1 norm if N is finite or l1 (the space of absolutely summable sequences) if N is infinite (thus in the latter case we identify N with N). If N=N, we assume that all matrices in (4) represent bounded operators from l1N to l1N. Alongside (4), we consider the simplified problem

    tuϵ(x,t)+ϵ1Vxuϵ(x,t)=0,x(0,1),t0,uϵ(x,0)=˚u(x),uϵ(0,t)=(I+ϵB)uϵ(1,t). (5)

    We will be working in X=L1([0,1],l1N). We define Aϵ as the realization of the differential expression Aϵ=diag(ϵ1vjx)jNM+R on the domain D(Aϵ)={uW11([0,1],l1N);u(0)=(I+ϵB)u(1)}, see [13]. In line with the interpretation of the model, we assume that I+ϵB0. Further, A0,ϵ is the realization of A0,ϵ=diag{ϵ1vjx}jN on the same domain. We assume that if N is infinite, then there are numbers vmin and vmax such that

    0<vminvjvmax<+,jN. (6)

    If N is finite, the fact that for each ϵ>0 the operator (A0,ϵ,D(Aϵ)) generates a semigroup, denoted by (etA0,ϵ)t0, follows from [5,Theorem 3.1]. However, the argument used in op.cit is purely norm dependent and can be repeated for countable N as long as B is bounded and (6) is satisfied, see also [13]. Then the boundedness of M and R allows for the application of the Bounded Perturbation Theorem, [14,Theorem Ⅲ 1.3], which gives the generation of (etAϵ)t0 by (Ae,D(Aϵ)).

    The paper is organized as follows. In Section 2 we show the convergence of the resolvents of (4) as ϵ0+ and thus, by the Trotter-Kato theorem, the convergence of semigroups (etAϵ)t0 to the age independent semigroup generated by VBM+R, but only for initial values that are constant for each jN. Such a convergence is often referred to as the regular convergence of semigroups, [10]. This result is not fully satisfactory as often singularly perturbed semigroups, possibly corrected by initial or boundary layers, converge to the limit semigroup for all initial conditions, see [6,7]. In Section 3 we show that in this case, in general it is impossible to achieve such a result. However, if we restrict our attention to the macroscopic characteristic of the model; that is, the observable total size of each subpopulation j, obtained from the solution to (5), then the situation changes. In Section 4 we prove that if the maturation times in each subpopulation are natural multiples of some fixed reference time, then, for arbitrary initial values ˚u, the population sizes obtained from the solution to (5) by integration over (0,1), converge to the solution to (2) that emanates from the initial condition 10˚u(x)dx. This extends a similar result from [6] obtained for velocities independent of jN. It is worthwhile to note that an analogous result using Banach algebra's techniques has been recently obtained in [11].


    2. Regular convergence

    Lemma 2.1.   The operators (Ae,D(Aϵ)) generate equibounded C0-semigroups on X.

    Proof. We begin with (A0,ϵ,D(Aϵ)). As we mentioned earlier, (A0,ϵ,D(Aϵ)) generates a C0 semigroup for each ϵ>0 follows from [5,Theorem 3.1]. Clearly, if for each ϵ>0 the semigroup (etA0,ϵ)t0 is contractive, then there is nothing to prove.

    In the general case, we rewrite the main formulae from the proof of [5,Theorem 3.1], specified for (5). First, we solve

    λϵuϵ,j+vjxuϵ,j=ϵfj,jN,x(0,1), (7)

    with (uϵ,j)jN=uϵD(A0,ϵ). The general solution is

    uϵ(x)=Eϵλ(x)cϵ+ϵV110Eϵλ(xs)f(s)ds, (8)

    where cϵ=(cϵ,j)jN is an arbitrary vector and Eϵλ(s)=diag(eϵλvjs)jN. Then, using the boundary condition uϵ(0)=(I+ϵB)uϵ(1), we obtain

    (I(I+ϵB)Eϵλ(1))cϵ=ϵ(I+ϵB)V110Eϵλ(1s)f(s)ds. (9)

    If ϵ is fixed, Eϵλ(1) can be made arbitrarily small by choosing large λ. Then cϵ is uniquely defined by the Neumann series and hence the resolvent of A0,ϵ exists.

    Since I+ϵB0, we can work with f0. Adding together the rows in (9) we obtain

    jNcϵ,j=jN(1+ϵbj)eϵλvjcϵ,j+ϵjN1+ϵbjvj10eϵλvj(s1)fj(s)ds, (10)

    where bj=iNbij<+ for any jN (by assumption that B is a bounded operator on l1N). We renorm X with uv=jNv1juj, which is equivalent to the standard norm by (6). Then, by integrating (8), we obtain

    uϵv=1λjNcϵ,jeϵλvjbj+ϵλjNbjvj10eϵλvj(s1)fj(s)ds+1λfv, (11)

    see [5,Theorem 3.1] for details. The case when bj0 for all jN leads to a contractive semigroup for each ϵ>0 and the equiboundedness is obvious. Otherwise, as in op. cit., we can assume that each bj is nonnegative. Then the generation is achieved by the application of the Arendt-Batty-Robinson theorem [2,3]. However, to prove equiboundedness of (etAϵ)t0 we need to understand how the Hille-Yosida estimates are obtained in this theorem.

    Using, for instance, the proof given in [3,Theorem 3.39], a densely defined resolvent positive operator T on a Banach lattice X generates a positive semigroup if there are λ0>s(T) (the spectral bound of T) and c>0 such that for any nonnegative xX we have R(λ0,T)xcx. In the proof one defines S=TωI, where s(T)<ωλ0 and then the Hille-Yosida estimate for S is obtained as

    λnR(λ,S)nxc1R(0,S)x=c1R(ω,T)x,λ>0. (12)

    Hence, we have to show that s:=supϵ>0{s(A0,ϵ)}< (and thus, by (11), we can take c=λ1 for any fixed λ>s) and that for some ω>s the family {R(ω,A0,ϵ)}ϵ>0 is equibounded. For this, let us return to (9) and estimate the Neumann series for (I(I+ϵB)Eϵλmbda(1))1. We have

    (I(I+ϵB)Eϵλ(1))1n=0(1+ϵB)neϵλnvmaxn=0eϵBneϵλnvmax=11eϵ(Bv1maxλ), (13)

    provided λ>Bvmax.

    Next, using l'Hôspital's rule, we find

    limϵ0+ϵ1eϵ(Bv1maxλ)=1v1maxλB

    and hence ϵ(I(I+ϵB)Eϵλ(1))1L1 for some constant L1 (depending on λ), yielding

    cϵ=ϵ(I(I+ϵB)Eϵλ(1))1(I+ϵB)V110Eϵλ(1s)f(s)dsL2f (14)

    for some constant L2. Let us fix ω>vmaxB. Using (8) and (14), we see that there is a constant L, independent of ϵ such that

    R(ω,A0,ϵ)L. (15)

    Then, using (11), the equivalence of the norms v and and R(λ,A0,ϵωI)=R(λ+ω,A0,ϵ), we write (12) as

    R(λ,A0,ϵ)nM(λω)n (16)

    for some constant M and λ>ω. Thus the operators (A0,ϵ,D(Aϵ)) generate semigroups satisfying

    etA0,ϵMeωt

    with constants M and ω independent of ϵ.

    The result for Aϵ follows from [14,Theorem Ⅲ.1.3].

    Now let us pass to the question of the convergence of the resolvents. We introduce the projection operator P:Xl1N by

    Pf=10f(s)ds=(10f1(s)ds,,10fn(s)ds,). (17)

    Theorem 2.2.  If λ>ω+QLω1, where ω and L are defined in (15) and (16), and Q=M+R, then

    limϵ0+R(λ,Aϵ)=R(λ,VB+Q)P. (18)

    in the uniform operator topology.

    Proof. By the previous proof, the resolvent of A0,ϵ is given by

    [R(λ,A0,ϵ)f](x)=Eϵλ(x)cϵ+ϵV110Eϵλ(xs)f(s)ds,λ>vmaxB, (19)

    where

    cϵ=ϵ(I(I+ϵB)Eϵλ(1))1(I+ϵB)V110Eϵλ(1s)f(s)ds. (20)

    We observe that for any α[0,1] the matrix Eϵλ(α) has the following Taylor expansion

    Eϵλ(α)=I+ϵR0(α)=IϵλαV1+ϵ2R1(α), (21)

    where, using the integral form of the reminders, we find

    R0(α)λαvmaxR1(α)λ2α22v2max.

    First we see that

    ϵV110Eϵλ(xs)f(s)dsϵV11010(eλϵ(xs)vjfj(s))jNdsdxϵV11010f(s)dsdxϵV1f

    and hence the last term in (19) converges to zero as ϵ0+.

    Next, using the second equality in (21) with α=1, we have for λ>vmaxB

    ϵ(I(I+ϵB)Eϵλ(1))1=ϵ(I(I+ϵB)(IϵλV1+ϵ2R1))1=(λV1BϵR1+ϵλBV1ϵ2BR1)1.

    Since λV1B=V1(λIVB) is invertible for λ>VB and vmaxBVB, we use [1,Proposition 7.2] to obtain

    limϵ0+ϵ(I(I+ϵB)Eϵλ(1))1=(λVB)1V. (22)

    Next, using the first equation in (21) we see that

    10Eϵλ(1s)f(s)ds10f(s)dsϵf10R0(1s)dsϵλfvmax10(1s)ds=ϵλf2vmax.

    Thus

    limϵ0+cϵ=(λVB)110f(s)ds. (23)

    Finally, treating cEϵλ(x)c as the operator from l1N to X, we estimate

    Eϵλ(x)cc=10(Eϵλ(x)I)cdxϵc10R0(x)dxϵλ2vmaxc.

    This actually shows that the operators converge in the uniform operator norm. Combining all estimates and using the projection operator P we find that

    limϵ0+R(λ,A0,ϵ)=(λVB)1P. (24)

    From (16) and (15) we have, in particular,

    R(λ,A0,ϵ)R(ω,A0,ϵ)c(λω)Lω(λω). (25)

    for some fixed ω>vmaxB and arbitrary λ>ω. Since Q=M+R is bounded,

    (QR(λ,A0,ϵ))nQnLnωn(λω)n.

    Hence, for A0,ϵ=A0+Q we have

    R(λ,Aϵ)=R(λ,A0,ϵ)n=1(QR(λ,A0,ϵ))n (26)

    and the series converges uniformly in ϵ for λ>ω+QLω1. Since the operators B,V,Q are independent of x, they commute with P and, by P2=P, we have

    limϵ0+R(λ,Aϵ)=R(λ,VB)Pn=1(QR(λ,VB)P)n=R(λ,VB+Q)P.

    Corollary 1.  If ˚ul1N (that is, the initial condition is independent of x), then

    limϵ0+etAϵ˚u=et(VB+Q)˚u (27)

    almost uniformly (that is, uniformly on compact subsets) on [0,+).

    Proof. According to the version of the Trotter-Kato approximation theorem given in [9,Theorem 8.4.3], if the resolvents of the generators of an equibounded family of semigroups (strongly) converge to an operator Rλ, then Rλ is the resolvent of the generator of a semigroup on the closure of its range. Here, the limit operator is the resolvent of the bounded operator VB+Q composed with the projection P:Xl1N. Thus, restricted to l1N, the range of R(λ,VB+Q)P equals the range of R(λ,VB+Q) which is l1N. Hence, (27) follows from the Trotter-Kato theorem.


    3. A counterexample

    This result is not very satisfactory. In asymptotic theory, [6,7,10], the convergence obtained in Corollary 1 is referred to as the regular convergence. However, typically it is possible to extend the convergence to initial data from the whole space, albeit at the cost of losing the convergence at t = 0; or adding necessary initial or boundary layers. The following example shows that this is impossible to achieve in our context. Consider the scalar problem

    tuϵ(x,t)+ϵ1xuϵ(x,t)=0,x(0,1),t0,uϵ(x,0)=˚u(x),uϵ(0,t)=(1+ϵb)uϵ(1,t),

    where bR. It is easy to see that if uϵ(x,t)=[etA0,ϵ˚u](x), then for t satisfying nϵt<(n+1)ϵ, so that n=t/ϵ, we have

    uϵ(x,t)={(1+ϵb)te+1˚u(x+te+1te)for0xtete,(1+ϵb)te˚u(x+tete)fortetex1. (28)

    Then

    limϵ0+(1+ϵb)n=limϵ0+((1+ϵb)1ϵb)t/ϵϵb=ebt,

    where we used

    limϵ0+tϵϵ=t. (29)

    The above is obvious for t=0 and for t>0 it follows from

    nn+1teϵt1

    and n with ϵ0.

    At the same time, let us consider t=1 and ϵ=1/k. Then we obtain

    u1k(x,1)=(1+1kb)k˚u(x),0x1,

    while for ϵ=22k+1 we have

    u22k+1(x,1)={(1+22k+1b)k+1˚u(x+12)for0x<12,(1+22k+1b)k˚u(x12)for12x1.

    From this it follows that

    limkeA0,1k˚u=eb˚u

    and

    limkeA0,22k+1˚u=eb˚v

    in L1([0,1], where ˚v(x)=˚u(x+1/2) for x[0,1/2) and ˚v(x)=˚u(x1/2) for x[1/2,1]. Thus (etAϵ)t0 does not converge as ϵ0+ for all initial conditions. However, it is easy to see that

    limϵ0+etA0,ϵ˚u=ebt˚u,

    provided ˚u is a constant, in accordance with Corollary 1.


    4. A version of irregular convergence

    As demonstrated in Section 3, we should not expect the convergence of (etAϵ)t0 for initial conditions which are not constant for each population. However, under certain additional assumptions we can derive a stronger version of convergence than that of Corollary 1, that is of relevance to the problem at hand. In fact, we are interested in approximating the solutions to (4) (or (5)) by solutions to the system of ODEs (2). The solution of (2) gives the total size of each subpopulation, while the solution to (4) (or (5)) gives the density in each subpopulation. The total number of individuals in each subpopulation can be calculated by integrating the density. Hence, we can ask how well the total population in each subpopulation, calculated from the solution of (4) (or (5)) can be approximated by the solution to (2). Using the notation of Section 2, the problem can be expressed as follows: does

    limϵ0+PetAϵ˚u=etHP˚u (30)

    hold for some some matrix H?

    In this section we shall focus on problem (5) and adopt the assumption from [17] that the speeds vj, jN, are linearly dependent over the field of rational numbers Q or, in other words,

    vRjNvvj=ljN. (31)

    In our interpretation of the model, this corresponds to the situation that the maturation times τj=1/vj in each subpopulation are natural multiples of some fixed reference maturation time τ=1/v. We observe that (6) implies that the set of different velocities is finite.

    Condition (31) allows the problem to be transformed into an analogous problem with unit velocities. Such a transformation appeared in [17] (and in a more detailed version in [20]) in the context of transport on networks and thus, even though (5) is not necessarily related to the network transport, see [4], its interpretation as a network problem allows for a better description of the construction.

    Using the graph theoretical terminology, we identify the jth subpopulation with an oriented edge ej parametrized by x(0,1), with ageing corresponding to moving from the tail of ej, associated with 0, to the head associated with 1, and denote G={ej}jN. Let Q be the graph with the set of vertices, V(Q), equal to G and the adjacency matrix I+ϵB. We note that, in general, Q is not the line graph as I+ϵB allows for the construction of the vertices connecting the edges ej so that G becomes a graph only in very special cases, [4].

    To proceed with the construction, first we re-scale time as τ=vt and, for each jN, we re-parameterize each edge ej by y=ljx. This converts (5) into a problem with the unit velocity for each jN, but with the equations defined on (0,lj). However, since each lj is a natural number, we subdivide each interval (0,lj) into lj intervals of unit length. The kth subinterval in (0,lj) is identified with the edge ej,k. This creates from G the set G1={{ej,k}1klj}jN consisting of, say, M edges. Then, as in the previous paragraph, we define Q1 to be the graph with V(Q1)=G1. Its adjacency matrix must take into account the connections between the old edges ej, determined by I+ϵB, and the connections across the points subdividing the old edges. More precisely, consider a function f on G that is continuous on each ej. This function is transformed into a function φ on G1, the components of which are required to have the same values at the head of ej,k and the tail of ej,k+1, k=1,,lj1,jN. Then it is easy to see that the adjacency matrix of Q1 satisfying these conditions is given by

    T+ϵC=(T10000Tj0)+ϵ(C11C1jCj1Cjj).

    Here, Tj is a lj×lj dimensional matrix which is either a scalar 1 if lj=1, or a cyclic matrix, and Cij is an li×lj matrix, given, respectively, by

    Tj=(0001100000010),Cij=(000bij000000000).

    Summarizing, we converted (5) into

    tυϵ(x,t)+ϵ1vxvϵ(x,t)=0,x(0,1),t0,vϵ(x,0)=˚v(x),vϵ(0,t)=(T+ϵC)vϵ(1,t). (32)

    Since (32) has the same structure as (5), there is a semigroup (etA0,ϵ)t0 solving it.

    To be more precise, the above construction defines an operator fφ=Sf, where φ=(ϕj,s)jN,1slj, f=(fj)jN and, for s{1,,lj},

    ϕj,s(y)=fj|[s1lj,slj)(s+y1lj). (33)

    It is easy to see that the inverse f=S1φ is defined by

    fj(x)=ϕj,s(ljx+1s),x[s1lj,slj),s{1,,lj},jN. (34)

    By direct calculation, see also [20], S:XX:=L1([0,1],l1M) is an isomorphism such that we have the similarity relation

    etA0,ϵf=S1etvA0,ϵSf,fX. (35)

    The motivation behind (35), see [13] and [20,Proposition 4.5.1], is the fact that for any φX

    (etvA0,ϵφ)(x)=(T+ϵC)nφ(n+xvte),nN,0n+xvte<1, (36)

    with (etvA0,ϵφ)(x)=φ(xvt/ϵ) for vt/ϵx<1.

    Let l=lcm{lj}jN. We observe that Tl=I and

    (T+ϵC)l=I+ϵ˜C+ϵ2D, (37)

    where

    ˜C=li=0Tl1iCTi.

    For any KN, let PK be the projection from L1([0,1],l1K) to l1K, given by (17).

    The next result is not strictly necessary but it relates operators on G to those on G1 and introduces in a natural way the projection Π that plays an essential role in the main theorem.

    Proposition 1.  For λ>vmaxB, we have

    (λvl1˜C)1ΠPMφ=S(λVB)1PNS1φ, (38)

    where

    Π=l1l1i=0Ti. (39)

    Proof. The estimate (13) carries over to this case by (35), which also gives

    R(λ,vA0,ϵ)φ=SR(λ,A0,ϵ)S1φ,φX,λ>vmaxB, (40)

    and, by Theorem 2.2 and the continuity of S,

    limϵ0+R(λ,vA0,ϵ)φ=S(λVB)1PNS1φ. (41)

    To find the limit resolvent in terms of ˜C, we modify the calculations from Theorem 2.2. The only different part is related to the calculation of

    cϵ=ϵ(I(T+ϵC)Eϵλ(1))1(T+ϵC)10Eϵλ(1s)f(s)ds, (42)

    where here Eϵλ(s)=eϵλvsI. We have, for λ>vmaxB,

    (I(T+ϵC)Eϵλ(1))1=k=0eϵλv1k(T+ϵC)k=l1i=0(T+ϵC)i(j=0(T+ϵC)ljeϵλv1(lj+i))=j=0(I+ϵ˜C+ϵ2D)jEϵlλ(j)(l1i=0(T+ϵC)ieϵλv1i).

    Hence, as in (22) with V=vl1I,

    limϵ0+ϵ(I(T+ϵC)Eϵλ(1))1=(λvl1˜C)1(l1l1i=0Ti)=(λvl1˜C)1Π.

    Since T is block diagonal with a finite number of finite dimensional blocks Tj (different from 1), we can use the finite dimensional theory to claim, by [19,p. 633], that Π is the projector onto the eigenspace of T corresponding to the eigenvalue λ=1 along the range of IT. The action of each block

    Πj=l1l1j=0Tij=l1jlj1j=0Tij

    amounts to

    Πjvj=1lj(ljr=1υj,r,,ljr=1υj,r). (43)

    Then the operator S1Π transforms functions which are constant on each edge of G1 to functions which are constant on each edge of G.

    Now, proceeding as in the proof of Theorem 2.2, we find

    limϵ0+R(λ,vA0,ϵ)φ=(λvl1˜C)1(l1l1i=0Ti)10φ(s)ds=(λvl1˜C)1ΠPMφ,

    where we used

    (l1i=0Ti)T=l1i=0Ti, (44)

    by periodicity. This, combined with (40), ends the proof.

    Using (43) and (34), we see that

    PNS1φ=10[S1φ](x)dx=(l1jljs=110ϕj,s(y)dy)jN=S1ΠPMφ. (45)

    Theorem 4.1.  For any fX we have

    limϵ0+PNetA0,ϵf=etVBPNf. (46)

    Proof. Let us write fX as

    f=PNf+fPNf=PNf+w,

    where PNfl1N and PNw=0.

    By Corollary 1 and the continuity of PN,

    limϵ0+PN[etA0,ϵPNf]=PNetVBPNf=etVBPNf.

    Hence, by linearity, it suffices to show that

    limϵ0+PN[etA0,ϵw]=0, (47)

    provided PNw=0. By (45), we have

    PN[etA0,ϵf]=PNS1[etvA0,ϵSf]=S1ΠPM[etvA0,ϵSf],fX. (48)

    Further, for n1vt/ϵn and φX, we have

    PMetvA0,ϵφ=(T+ϵC)nvtϵn+10φ(n+xvtϵ)dx+(T+ϵC)n11vtϵn+1φ(n1+xvtϵ)dx, (49)

    hence, by (44),

    ΠPMetvA0,ϵφ=Π(T+ϵC)n110φ(z)dz+ϵΠC(T+ϵC)n11nvtϵφ(z)dz.

    Let us denote (T+ϵC)jTj=ϵRj. Then, again by (44),

    Π(T+ϵC)n1=1ll1j=0Tj(T+ϵC)n1=1ll1j=0((T+ϵC)n1+jϵRj(T+ϵC)n1)=1ll1j=0((T+ϵC)n1(Tj+ϵRj)ϵRj(T+ϵC)n1)=(T+ϵC)n1Π+ϵ((T+ϵC)n1RR(T+ϵC)n1), (50)

    where R=1ll1j=0Rj. Since S is an isomorphism, using (45) we see that PNw=0 implies ΠPMSw=0, hence (T+ϵC)n1ΠPMSw=0. Thus (49) and (50) yield

    limϵ0ΠPMetvA0,ϵSw=limϵ0ϵΠC(T+ϵC)n11nvtϵSw(z)dzxx+limϵ0ϵ((T+ϵC)n1RR(T+ϵC)n1)PMSw=0,

    which proves (47).


    Acknowledgments

    The authors are indebted to Professor Adam Bobrowski for taking interest in the paper, suggesting corrections to its early version and many stimulating discussions.


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