T periodic solutions in the 2D quasispecies model

for cancer growth dynamics with multiple

different delays.

Abstract
This article investigates the existence of positive periodic solutions for
a system of equations of the form

2
X
x′i (t) = fj (t)ψ(xj (t − τj (t)))(Qji (t) − xi (t)), i = 1, 2.
j=1

MSC 2020 Classification : 34K13, 47H11

Key words : Differential delay equation; Periodic solutions; Degree theory

1
 1 Introduction and main result
sec_1
In this paper, using topological Leray-Schauder degree arguments, we study
the existence of at least one positive T -periodic solution for delay differential
equations system having the form

2
X
x′i (t) = fj (t)ψ(xj (t − τj (t)))(Qji (t) − xi (t)), i = 1, 2,
j=1   (1) Ec_pri
xi (t) = ϕi (t), t ∈ − max {τi (t) : i = 1, 2}, 0 , i = 1, 2,
t∈[0,T ]

where ϕj , τj , fj , j = 1, 2, are positive T -periodic continuous functions, ψ ∈

C([0, 1], [0, 1]) such that if ψ(x0 ) = 0 then x0 = 0 or x0 = 1, and Qji ∈
C([0, T ], [0, 1]), i = 1, 2, j = 1, 2, are T -periodic functions satisfying the follow-
ing hypothesis
X2
Qij (t) = 1, i = 1, 2, ∀t ∈ [0, T ].
j=1

To better express our hypotheses we use the following notations

1. As usual, we write CT := {θ ∈ C([0, T ], R) : θ(0) = θ(T )}

mθ = min θ(t), Mθ = max θ(t),

t∈[0,T ] t∈[0,T ]

Z T
1
θ := θ(t)dt,
T 0

P [θ1 , θ2 ] := (θ1 (0), θ2 (0))⊤ , Q[θ1 , θ2 ] := (θ1 , θ2 )⊤ ,

Z t Z t ⊤
K[θ1 , θ2 ] := θ1 (s)ds, θ2 (s)ds ,
0 0
⊤
where v stands for the transpose of the vector v.2
2. We denote as:

Rn = {(x1 , x2 , ..., xn ) ∈ Rn : x1 + x2 + ... + xn = 1}.

f1
γn = max {τj (t) : i = 1, n}, r := , q := Q11 , p := Q21 ,
t∈[0,T ] f2
η ∈ R tal que 0 < η < min {p(t), q(t)},
t∈[0,T ]

ν ∈ R tal que max {p(t), q(t)} < ν < 1,

t∈[0,T ]

N (x, y) :=(qf1 − 2f1 ψ(x) − f2 ψ(y))(f2 − pf2 − 2f2 ψ(y) − f1 ψ(x))

− (f1 − qf1 − f1 ψ(y))(pf2 − f2 ψ(x))

2
 To express our result we need to add the following conditions:
[S]: The system

qf1 ψ(x) + pf2 ψ(y) − x(f1 ψ(x) + f2 ψ(y)) =0

(2) sist
(f1 − qf1 )ψ(x) + (f2 − pf2 )ψ(y) − y(f1 ψ(x) + f2 ψ(y)) =0

has at least one solution in ]η, ν[×]0, 1[.

Xk
[C]: sign(N (xi , yi )) ̸= 0 where (xi , yi ), i = 1, k are solutions of the system
i=1
(2) in ]η, ν[×]0, 1[.
Now we can state our main result:
TeoP Theorem 1. Assume [C], [S]. If 0 < p(t) < 1, 0 < q(t) < 1 for all t ∈ [0, T ]
and ϕ1 (0) + ϕ2 (0) = 1. Then problem (1) admits at least one T -periodic positive
solution such that
η < x1 (t) < ν 0 < x2 (t) < 1
and x1 (t) + x2 (t) = 1 for all t ≥ 0.
Teo2 Theorem 2. Let x1 , x2 be positive T-periodic solutions of the system (1) in the
interval ]0, 1[. Then we have the following cases:
• If Mq > Mp , then Mx1 < Mq and mx2 > 1 − Mq .
• If Mp > Mq , then Mx1 < Mp and mx2 > 1 − Mp .
• If Mp = Mq , then Mx1 ≤ Mp and mx2 ≥ 1 − Mp .
• If mq < mp , then mx1 > mq and Mx 2 < 1 − m q .
• If mp < mq , then mx1 > mp and Mx2 < 1 − mp .
• If mp = mq , then mx1 ≥ Mp and mx2 ≥ 1 − mp .

2 Abstract setting
sec_2
We are about to rewrite the problem of finding T -periodic solutions for (1) as
a fixed-point problem for an relatively compact operator.
We define the operator

A : CT ×CT → CT ×CT , A[x1 , x2 ] = P [x1 , x2 ]+QN [x1 , x2 ]+K(I−Q)N [x1 , x2 ],

where
 2
X

 fj (t)ψ(xj (t − τj (t)))(Qj1 (t) − x1 (t)) 
j=1
 
N [x1 , x2 ](t) = 
 2


X
fj (t)ψ(xj (t − τj (t)))(Qj2 (t) − x2 (t))
 
j=1

3
 We consider next the operator A : CT × CT → CT × CT . In this way the
operator is completely continuous and the Leray-Schauder Degree applies. Also,
in this setting the periodic boundary value problem for (1) becomes equivalent
to the fixed-point problem for an operator equation

(x1 , x2 )⊤ = A[x1 , x2 ], (x1 , x2 ) ∈ CT × CT . (3) opecu

The key to proving the Theorems 1 is to prove that the degree of the operator
I − A on a proper open set is nonzero.
We defined the open bounded set

Ω := {(x1 , x2 ) ∈ CT × CT : η < x1 (t) < ν, 0 < x2 (t) < 1, ∀t ∈ [0, T ]} .

To do this we first define the following homotopy

H : [0, 1] × CT × CT → CT × CT ,

H[λ, x1 , x2 ] := (x1 , x2 )⊤ − (P [x1 , x2 ] + QN [x1 , x2 ] + λK(I − Q)N [x1 , x2 ])

Before jumping into the mathematical details, it will be convenient, to define
Σ as the set of possible solutions of the homotopy H[λ, x1 , x2 ] = 0, λ ∈ [0, 1].
Below we will prove first that Σ ⊆ Ω.
cerosfron Remark 1. The system of equations (2) has no solutions in (x1 , x2 ) ∈ R2 ∩ ∂Ω
has no solution.
vari_inva Proposition 1. If (ϕ1 (0), ϕ2 (0), ..., ϕn (0)) ∈ Rn then Rn is an invariant man-
ifold of delay differential equations system
n
X
x′i (t) = fj (t)ψ(xj (t − τj (t)))(Qji (t) − xi (t)), i = 1, n,
j=1
(4) Sist_Gen
xi (t) = ϕi (t), t ∈ [−γn , 0] , i = 1, n.

Proof. Let (x1 (t), x2 (t), ..., xn (t)) ∈ C 1 ([0, T ], Rn ) is a solution of the system
(4). Observe that
n
! n
! n
d X X X
xi (t) = 1 − xi (t) fj (t)ψ(xj (t − τj (t))).
dt i=1 i=1 j=1

n
X
If we consider z(t) = xi (t) and considering the method of steps in system
i=1
(4), this system reduces for t ∈ [0, γn ] in the ordinary differential equation
n
X
z ′ (t) = (1 − z(t)) fj (t)ψ(ϕj (t − τj (t))), (5) EDO
j=1

such that z(0) = 1, then by the existence and uniqueness theorem we have that
z(t) = 1 for t ∈ [0, γn ], applying again the method of the steps for t ∈ [γn , 2γn ]

4
 we obtain the equation (5) with the initial condition z(γn ) = 1 from where again
we have that z(t) = 1 for t ∈ [γn , 2γn ]. If we continue in this way by induction
Xn
we obtain that z(t) = xi (t) = 1 for all t ≥ 0, this concludes the proof..
i=1

cots1 Lemma 1. Assume that all the hypotheses of Theorem 1 are verified. Then
Σ ⊆ Ω for every λ ∈ [0, 1[ for t ∈ [0, T ]
Proof. We assume, on the contrary, that there exists λ ∈ [0, 1[ and (x1 , x2 ) ∈ Σ
such that θ ∈ ∂Ω. If λ = 0, from the definition of H we obtain that (x1 , x2 ) ∈
R2 ∩ ∂Ω and satisfies the system of equations (2), this contradicts the Remark
1. If λ ∈]0, 1[ from the definition of H we obtain
2
X
x′1 (t) = λ fj (t)ψ(xj (t − τj (t)))(Qj1 (t) − x1 (t))
j=1
2 (6) ecT1
X
x′2 (t) =λ fj (t)ψ(xj (t − τj (t)))(Qj2 (t) − x2 (t)),
j=1

If we take tx , ty ∈ [0, T ] such that x′1 (tx ) = 0 and x′2 (ty ) = 0, from (6) we
get

ψ(x2 (tx − τ2 (tx )))(p(tx ) − x1 (tx )) = r(tx )ψ(x1 (tx − τ1 (tx )))(x1 (tx ) − q(tx )), (7) x’

ψ(x2 (ty −τ2 (ty )))(1−p(ty )−x2 (ty )) = r(ty )ψ(x1 (ty −τ1 (ty )))(x2 (ty )−1+q(ty )).
(8) y’
We have the following cases
• If x1 (tx ) = Mx = ν or x(tx ) = mx = η, then from (7) we obtain

0 ≥ ψ(x2 (tx − τ2 (tx )))(p(tx ) − ν) = r(tx )ψ(x1 (tx − τ1 (tx )))(ν − q(tx )) > 0,
0 ≤ ψ(x2 (tx − τ2 (tx )))(p(tx ) − η) = r(tx )ψ(x1 (tx − τ1 (tx )))(η − q(tx )) < 0

respectively, this implies a contradiction in both cases.

• If x2 (ty ) = My = 1 or x2 (ty ) = my = 0, then from (8) we obtain

0 ≥ ψ(x2 (ty − τ2 (ty )))(−p(ty )) = r(ty )ψ(x1 (ty − τ1 (ty )))q(ty ) > 0,
0 ≤ ψ(x2 (ty − τ2 (ty )))(1 − p(ty )) = r(ty )ψ(x1 (ty − τ1 (ty )))(−1 + q(ty )) < 0

respectively, this implies a contradiction in both cases.

Proof of Theorem 1. Applying Lemma 1 we deduce that H is an admissible

homotopy, and hence,

dLS (I − A, Ω, 0) = dLS (H[1, ·], Ω, 0)

= dLS (H[0, ·], Ω, 0)

5
 Then since (I − H[0, ·])(Ω) ⊆ R2 , we obtain that
dLS (H[0, ·], Ω, 0) = dB (H[0, ·]Ω∩R2 , Ω ∩ R2 , 0)
By using Brouwer degree theory we have that

dB (H[0, ·]Ω∩R2 , Ω ∩ R2 , 0) = dB (−QN [·]Ω∩R2 , Ω ∩ R2 , 0)

where −QN [x, y] = 0 is given by system (2).

From condition [S] we denote as (xi , yi ), i = 1, n the solutions of system (2)
in the open set Ω, then, by degree theory in finite dimension and condition [C]
we have that
n
X
dB (−QN [·]Ω∩R2 , Ω ∩ R2 , 0) = − sgn N (xi , yi ) ̸= 0
i=1

Therefore the system (1) has at least one solution, also considering Proposition
1 the proof of the Theorem is concluded.
Proof of Theorem 2. The demonstration will be done by cases:
• Let Mq > Mp . Suppose that Mx1 ≥ Mq , then from equation (7) we have
that
0 > ψ(x2 (tx −τ2 (tx )))(p(tx )−Mx1 ) = r(tx )ψ(x1 (tx −τ1 (tx )))(Mx1 −q(tx )) ≥ 0,
this is a contradiction. On the other hand, since Mq > Mp then 1 − Mp >
1 − Mq , and if we assume that mx2 ≤1−Mq , then from equation (8) we have
that
0 < ψ(x2 (ty −τ2 (ty )))(1−p(ty )−mx2 ) = r(ty )ψ(x1 (ty −τ1 (ty )))(mx2 −(1−q(ty ))) ≤ 0,
this is a contradiction.
The other cases are proved in a similar way. The proof of the Theorem is
concluded.

3 Application
app_mono
Equation (1) has been studied for multiple cases of ϕ, for example we mention
the following two cases:
2
X
x′i (t) = fj (t)xj (t − τj (t))(Qji (t) − xi (t)), i = 1, 2. (9) App1
j=1

2
X
x′i (t) = fj (t)xj (t − τj (t))(1 − xj (t − τj (t)))(Qji (t) − xi (t)), i = 1, 2. (10) App2
j=1

The applications of the Theorems 1 and 2 to these particular cases are:

6
Teoapp1 Theorem 3. Assume [C] and [S] are satisfied with ψ(x) = x. If 0 < p(t) < 1,
0 < q(t) < 1 for all t ∈ [0, T ] and ϕ1 (0) + ϕ2 (0) = 1. Then problem (9) admits
at least one T -periodic positive solution such that
min {p(t), q(t)} ≤ x1 (t) ≤ max {p(t), q(t)}
t∈[0,T ] t∈[0,T ]

1 − max {p(t), q(t)} ≤ x2 (t) ≤ 1 − min {p(t), q(t)}

t∈[0,T ] t∈[0,T ]

and x1 (t) + x2 (t) = 1 for all t ≥ 0.

coro1 Corollary 1. If f1 , f2 are constant functions, 0 < p(t) < 1, 0 < q(t) < 1 for
all t ∈ [0, T ], p = q and ϕ1 (0) + ϕ2 (0) = 1. Then problem (9) admits at least
one T -periodic positive solution such that
min {p(t), q(t)} ≤ x1 (t) ≤ max {p(t), q(t)}
t∈[0,T ] t∈[0,T ]

1 − max {p(t), q(t)} ≤ x2 (t) ≤ 1 − min {p(t), q(t)}

t∈[0,T ] t∈[0,T ]

and x1 (t) + x2 (t) = 1 for all t ≥ 0.

Teoapp2 Theorem 4. Assume [C] and [S] are satisfied with ψ(x) = x(1 − x). If 0 <
p(t) < 1, 0 < q(t) < 1 for all t ∈ [0, T ] and ϕ1 (0) + ϕ2 (0) = 1. Then problem
(10) admits at least one T -periodic positive solution such that
min {p(t), q(t)} ≤ x1 (t) ≤ max {p(t), q(t)}
t∈[0,T ] t∈[0,T ]

1 − max {p(t), q(t)} ≤ x2 (t) ≤ 1 − min {p(t), q(t)}

t∈[0,T ] t∈[0,T ]

and x1 (t) + x2 (t) = 1 for all t ≥ 0.

coro2 Corollary 2. If f1 , f2 are constant functions, 0 < p(t) < 1, 0 < q(t) < 1 for
all t ∈ [0, T ], p = q and ϕ1 (0) + ϕ2 (0) = 1. Then problem (10) admits at least
one T -periodic positive solution such that
min {p(t), q(t)} ≤ x1 (t) ≤ max {p(t), q(t)}
t∈[0,T ] t∈[0,T ]

1 − max {p(t), q(t)} ≤ x2 (t) ≤ 1 − min {p(t), q(t)}

t∈[0,T ] t∈[0,T ]

and x1 (t) + x2 (t) = 1 for all t ≥ 0.

Proof of Corollaries 1 and 2. The proof follows from applying Lemma 1, Propo-
sition 1 and observing that in both cases the only solution of system (2) is
(x1 , x2 ) = (q, 1 − q). Then we obtain for Corollaries 1 and 2 that N (q, 1 − q) =
(q(r − 1) + 1)2 ̸= 0 and N (q, 1 − q) = (q − 1)2 q 2 (r + 1)2 ̸= 0 respectively.

References
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the effect of diffusion, J. Math. Anal. Appl. 254(2001), 433-463.