In this paper we develop a four compartment within-host model of nutrition and HIV. We show that the model has two equilibria: an infection-free equilibrium and infection equilibrium. The infection free equilibrium is locally asymptotically stable when the basic reproduction number R0<1, and unstable when R0>1. The infection equilibrium is locally asymptotically stable if R0>1 and an additional condition holds. We show that the within-host model of HIV and nutrition is structured to reveal its parameters from the observations of viral load, CD4 cell count and total protein data. We then estimate the model parameters for these 3 data sets. We have also studied the practical identifiability of the model parameters by performing Monte Carlo simulations, and found that the rate of clearance of the virus by immunoglobulins is practically unidentifiable, and that the rest of the model parameters are only weakly identifiable given the experimental data. Furthermore, we have studied how the data frequency impacts the practical identifiability of model parameters.
Citation: Archana N. Timsina, Yuganthi R. Liyanage, Maia Martcheva, Necibe Tuncer. A novel within-host model of HIV and nutrition[J]. Mathematical Biosciences and Engineering, 2024, 21(4): 5577-5603. doi: 10.3934/mbe.2024246
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In this paper we develop a four compartment within-host model of nutrition and HIV. We show that the model has two equilibria: an infection-free equilibrium and infection equilibrium. The infection free equilibrium is locally asymptotically stable when the basic reproduction number R0<1, and unstable when R0>1. The infection equilibrium is locally asymptotically stable if R0>1 and an additional condition holds. We show that the within-host model of HIV and nutrition is structured to reveal its parameters from the observations of viral load, CD4 cell count and total protein data. We then estimate the model parameters for these 3 data sets. We have also studied the practical identifiability of the model parameters by performing Monte Carlo simulations, and found that the rate of clearance of the virus by immunoglobulins is practically unidentifiable, and that the rest of the model parameters are only weakly identifiable given the experimental data. Furthermore, we have studied how the data frequency impacts the practical identifiability of model parameters.
In this paper, we study the following quasi-linear bi-hyperbolic equation:
wtt+Δ2w−Δw=bf(−Δw),inΩ×[0,T), | (1.1) |
under the following dynamic boundary conditions,
w=0,∂Δw∂η=−aΔwt,inΓ×[0,T), | (1.2) |
and initial conditions
w(x,0)=w0(x),wt(x,0)=w1(x),x∈Ω, | (1.3) |
where a≥0, b≥0, t≥0, x∈Ω, Ω is an open bounded connected region in Rn (n≥1) with a smooth boundary Γ:=∂Ω, and η(x) represents an outer unit normal vector to the boundary Γ.
The Eq (1.1) represents a mathematical model of a wave process in a physical domain Ω over a time interval [0,T). This wave equation involves wtt as the second-time derivative representing acceleration over time, Δ2w as the second-order spatial Laplacian indicating wave irregularities, Δw as the first-order Laplacian reflecting propagation speed within the wave, and bf(−Δw) as a nonlinear term depicting wave interaction with its negative Laplacian. Overall, these equations and conditions provide a framework for understanding wave behavior, interactions at boundaries, and the evolution of waves from specified initial conditions within a physical space. Applications of such equations extend to various areas, including acoustics, electromagnetics, and mechanics, where wave phenomena play a crucial role in modeling and analysis.
First, we mention some known results of higher-order differential equations under dynamic boundary conditions related to the problems (1.1)–(1.3). Dynamic boundary conditions introduce dependencies on both time and space variables, influencing the behavior and evolution of solutions within specific domains. Recent research has highlighted the significance of dynamic boundary conditions in various mathematical contexts, particularly in studying wave propagation, heat transfer, fluid dynamics, and other physical phenomena. Notably, works by Vasconcellos and Teixeira [1] have explored the implications of dynamic boundary conditions on well-posedness. They considered, for n≤3, the following problem:
{utt+Δ2u−ϕ(∫Ω|∇u|2dx)Δu+g(ut)=0,onΩ×(0,T),u=∂u∂ν=0,onΓ×(0,T), |
where ϕ is a non-negative continuous real differentiable function, and g is a continuous non-decreasing real function. They proved the existence and uniqueness of global solutions. Guedda and Labani [2] studied the problem
{utt+Δ2u+δut−ϕ(∫Ω|∇u|2dx)Δu=f(u),onΩ×(0,T),u=0,Δu+p(x)∂ut∂ν=0,onΓ×(0,T), |
where p≥0 is a smooth function defined on the boundary of Ω. They studied the global nonexistence of solutions under certain conditions on f and ϕ. Later, Wu and Tsai [3] considered the initial boundary value problem for a Kirchhoff-type plate equation with a source term in a bounded domain. They established the existence of a global solution using an argument similar to that in [4]. Vitillaro conducted a study in 2017 focusing on dynamic boundary conditions. In this work [5], a wave equation with hyperbolic dynamic boundary conditions, interior and boundary damping effects, and supercritical sources was investigated.
Several authors have extensively studied blow-up phenomena and global nonexistence (see [4,6,7,8,9]). Levine [8] introduced the concavity method and investigated the nonexistence of global solutions with negative initial energy. Subsequently, Georgiev and Todorova [4] expanded upon Levine's work. In 2002, Vitillaro [10] further refined the results of Georgiev and Todorova for systems with positive initial energy. Vitillaro also explored blow-up phenomena for wave equations with dynamic boundary conditions in [9]. Additionally, Can et al. [6,7] investigated the blow-up properties of (1.1) under various boundary conditions, assuming non-positive initial energy. While their result is achieved by applying the Ladyzhenskaya and Kalantarov lemma [11], along with a generalized concavity method, our approach is based on the blow-up lemma by Korpusov [12], which is another application of the concavity method. In our study of problems (1.1)–(1.3), we obtained both a local existence result and a blow-up result under positive initial energy.
The paper is structured as follows. Section 2 provides essential definitions, theorems, and inequalities. In Section 3, we initially employ the Galerkin approximation method to investigate the existence of the corresponding linear problems (3.1)–(3.3). Subsequently, utilizing the contraction mapping principle, we establish the local existence and uniqueness of regular solutions for problems (1.1)–(1.3). Finally, in the last section, we deduce the blow-up solutions for problems (1.1)–(1.3) under the condition of positive initial energy.
The Sobolev space is defined by Wk,p(Ω):={u∈Lp(Ω):Dαu∈Lp(Ω),∀0≤|α|≤k} for 1≤p<∞, equipped with the following norm:
‖u‖Wk,p(Ω):=(∑0≤|α|≤k‖Dαu‖pLp(Ω))1/p. |
We denote by Hk(Ω)=Wk,2(Ω) the Hilbert-Sobolev space. Throughout this paper, we denote ‖.‖L2(Ω)=‖.‖2.
Definition 2.1. Let w(t) be a weak solution of the problem defined by Eqs (1.1)–(1.3). We define the maximal existence time T∞ as follows:
(ⅰ) If w(t) exists for 0≤T<∞, then T∞=+∞.
(ⅱ) If there exists a T0∈(0,∞) such that w(t) exists for 0≤T<T0, but does not exist at T=T0, then T∞=T0.
In order to prove the blow-up result, we will utilize the following lemma due to Korpusov.
Lemma 2.2. [12] Let ψ(t)∈C2(0,T) and consider the differential inequality
ψψ″−α(ψ′)2+γψ′ψ+βψ≥0,α>1,β≥0,γ≥0. |
Assume that the following conditions
ψ′(0)>γα−1ψ(0),and(ψ′(0)−γα−1ψ(0))2>2β2α−1ψ(0), |
hold with ψ(t)≥0, and ψ(0)>0. Then the time T>0 can not be arbitrarily large. That is,
T<T∞=ψ1−α(0)A−1, |
where T∞ is the maximal existence time interval for ψ(t) and
A2≡(α−1)2ψ−2α(0)[(ψ′(0)−γα−1ψ(0))2−2β2α−1ψ(0)], |
such that limt↑T∞ψ(t)=+∞.
Now, we state the assumptions on the function f:
(A1) f:H20(Ω)→L2(Ω) is locally Lipschitz with the Lipschitz constant Lf, that is, for every x∈H20(Ω), there exists a neighborhood V of x and a positive constant Lf depending on V such that
‖f(y)−f(z)‖2≤Lf‖y−z‖2, |
for each y,z∈V.
(A2) The function f with its primitive F(u)=∫u0f(s)ds has the property:
f(0)=0,uf(u)≥2(2γ+1)F(u), | (2.1) |
for all u∈R and for some positive real number γ.
Example 2.3. Consider the function f(u)=u2. This function satisfies property (2.1) based on the conditions f(0)=0 and the behavior of its primitive, F(u)=∫u0f(s)ds=∫u0s2ds=u33. Specifically, we can establish the inequality uf(u)=u3≥2(2γ+1)u33, which holds true for some γ≤14.
In this section, we delve into the local existence of solutions for the wave Eqs (1.1)–(1.3) employing the contraction mapping principle. Initially, we examine the following linear initial boundary value problem:
wtt+Δ2w−Δw=h(x,t),inΩ×[0,T), | (3.1) |
w=0,∂Δw∂η=−aΔwt,inΓ×[0,T), | (3.2) |
w(x,0)=w0(x),wt(x,0)=w1(x),x∈Ω. | (3.3) |
Lemma 3.1. Suppose that w0∈U, w1∈H, and h∈W1,2(0,T;L2(Ω)). Then, the problems (3.1)–(3.3) admit a unique solution w such that
w∈L∞(0,T;U),wt∈L∞(0,T;H), |
where U={w∈H20(Ω):∂Δw∂η|Γ=−aΔwt}, and H=H10(Ω)∩H2(Ω).
Proof. We initially employed the Galerkin approximation method to investigate the existence of solutions to this linear problem. Let (ϕn)n∈N be a basis in U, and Vn denote the subspace generated by ϕ1,...,ϕn (n=1,2,...). Consider wn(t)=∑ni=1rin(t)ϕi as the solution of the approximation problem corresponding to (3.1)–(3.3) for ϕ∈Vn. Then, we have:
∫Ωw″nϕdx+∫ΩΔϕΔwndx+∫Ω∇wn∇ϕdx=∫Ωh(x,t)ϕdx, | (3.4) |
with initial conditions satisfying
wn(0)≡n∑i=1(∫Ωw0ϕidx)ϕi→w0inU, | (3.5) |
w′n(0)≡n∑i=1(∫Ωw1ϕidx)ϕi→w1inH. | (3.6) |
First, we verify the existence of solutions to (3.4)–(3.6) on some interval [0,tn), 0<tn<T, and then use standard differential equations techniques [13] to extend the solution across the entire interval [0,T]. To achieve this, we need to establish the following a priori estimates.
Setting ϕ=2w′n(t) in (3.4), integrating over (0,t), and utilizing boundary conditions yield:
‖w′n(t)‖22+‖Δwn(t)‖22+‖∇wn(t)‖22≤‖w′n(0)‖22+‖Δwn(0)‖22+‖∇wn(0)‖22+2∫t0∫Ωh(x,t)w′n(t)dx. |
From this, we obtain:
‖w′n(t)‖22+‖Δwn(t)‖22+‖∇wn(t)‖22≤C0+∫t0(‖w′n(s)‖22+‖Δwn(s)‖22)dt, | (3.7) |
where C0=‖w′n(0)‖22+‖Δwn(0)‖22+‖∇wn(0)‖22+∫T0‖h‖22dt, and utilizing the estimate:
2|∫Ωh(x,t)w′n(t)dx|≤‖h‖22+‖w′n(t)‖22. | (3.8) |
The conditions (3.5) and (3.6), and the property of h imply that C0 is bounded. Now, for all 0≤t≤T, applying Gronwall's inequality in (3.7), we obtain
‖w′n(t)‖22+‖Δwn(t)‖22+‖∇wn(t)‖22≤M1, | (3.9) |
where M1 is a positive constant.
To estimate w″n(0) in L2-norm, we set t=0 in (3.4) and ϕ=2w″n(0):
‖w″n(0)‖22≤‖w″n(0)‖2[‖Δ2wn(0)‖2+‖Δwn(0)‖2+‖h‖2]. | (3.10) |
By employing (3.5) and (3.6), we find a positive constant M2 such that:
‖w″n(0)‖2≤M2. | (3.11) |
Next, we aim to establish an upper bound for ‖w″n(t)‖2. Replacing ϕ=2w″n(t) in (3.4) after differentiating it with respect to t gives
ddt[‖w″n(t)‖22+‖Δw′n(t)‖22+‖∇w′n(t)‖22]≤2∫Ωh′(x,t)w″n(t)dx. | (3.12) |
Hence, by integrating (3.12) over (0,t) and using the inequalities (3.8), (3.9) and (3.11), we obtain
‖w″n(t)‖22+‖Δw′n(t)‖22+‖∇w′n(t)‖22⏟=:Y(t)≤Y(0)+∫T0‖h′‖22⏟=:C1+∫t0(‖w″n(s)‖22+‖Δw′n(s)‖22)dt. | (3.13) |
Using Gronwall's inequality for the inequality
Y(t)≤C1+∫t0(‖w″n(s)‖22+‖Δw′n(s)‖22)dt, |
and (3.5) and (3.6), we can derive
‖w″n(t)‖22+‖Δw′n(t)‖22+‖∇w′n(t)‖22≤M3, | (3.14) |
for any t∈[0,T] with a positive M3, which is independent of n∈N. Using (3.9) and (3.14), we may conclude that
wi→wweak∗inL∞(0,T;H20(Ω)), | (3.15) |
w′i→w′weak∗inL∞(0,T;H), | (3.16) |
w′i→w′andw″i→w″weak∗inL∞(0,T;L2(Ω)). | (3.17) |
Thus, by taking the limit in (3.4) and utilizing the above convergences, we obtain:
∫T0∫Ω(wtt+Δ2w−Δw)uσdxdt=∫T0∫Ωh(x,t)uσdxdt, |
for all σ∈D(0,T) and for all u∈U. From the above identity, we have
wtt+Δ2w−Δw=h(x,t)inL∞(0,T;L2(Ω)), | (3.18) |
since w″,Δw and h∈L∞(0,T;L2(Ω)) and we deduce Δ2w∈L∞(0,T;L2(Ω)), so w∈L∞(0,T;U).
To prove the uniqueness of the solution, let w1 and w2 be two solutions of (3.1)–(3.3). Then v=w1−w2 satisfies
∫Ωv″(t)ϕdx+∫ΩΔvΔϕdx+∫Ω∇v∇ϕdx=0, | (3.19) |
for ϕ∈U. Also, we have
v(x,0)=0,v′(x,0)=0inΩ,andv(x,t)=0,∂Δv∂η=−aΔvtonΓ. |
Now, if we set ϕ=2v′(t) in (3.19), then we have
‖v′(t)‖22+‖∇v(t)‖22+‖Δv(t)‖22≤∫t0‖v′(s)‖22+‖∇v(s)‖22. |
By Gronwall's inequality, we conclude that
‖v′(t)‖2=‖Δv(t)‖2=‖∇v(t)‖2=0,∀t∈[0,T]. |
Therefore, we have uniqueness. Now, we establish the local existence of the problems (1.1)–(1.3).
Theorem 3.2. Suppose that f:H20(Ω)→L2(Ω), and that w0∈U, and w1∈H, then there exists a unique solution w with w∈L∞(0,T;U) and wt∈L∞(0,T;H).
Proof. Define the following space for T>0 and R0>0:
XT,R0={v∈L∞(0,T;U),vt∈L∞(0,T;H):e(v(t))≡‖vt(t)‖22+‖Δv(t)‖22≤R20,t∈[0,T]}. |
Then XT,R0 is a complete metric space with the distance
d(x,y)=sup0≤t≤T[‖Δ(x−y)‖2+‖(x−y)t‖2]12, | (3.20) |
where x,y∈XT,R0.
By Lemma 3.1, for any u∈XT,R0, the problem
wtt+Δ2w−Δw=bf(−Δu) | (3.21) |
has a unique solution w of (3.21). We define the nonlinear mapping Bu=w, and then, we shall show that there exists T>0 and R0>0 such that
(ⅰ) B:XT,R0→XT,R0,
(ⅱ) In the space XT,R0, the mapping B is a contraction according to the metric given in (3.20).
After multiplication by 2wt in Eq (3.21), and integration over Ω, we find
e1(w(t)):=∫t0[‖wt‖22+‖Δw‖22+‖∇w‖22]=2b∫t0∫Ωf(−Δu)wtdx⏟I1. | (3.22) |
Taking into account the assumption (A1) on f, we obtain
|I1|=2b∫t0∫Ωbf(−Δu)wt(t)dΩdt≤b∫t0‖f(−Δu)‖2.‖wt(t)‖2dt≤2bLf∫T0‖−Δu(t)‖2.‖wt(t)‖2+2b∫t0‖f(0)‖2⏟=0‖wt(t)‖2dt≤(4b2L2f+1)∫t0(‖Δu(t)‖22+‖wt(t)‖22)dt⏟≤e1(w(s)). |
Then, by integrating (3.22) over (0,t) and using the above inequality, we deduce
e1(w(t))≤e1(w0)+(4b2L2f+1)∫t0e1(w(s))ds. |
Thus, by Gronwall's inequality, we have
e1(w(t))≤e1(w0)e∫t04b2L2f+1. | (3.23) |
Therefore, if the parameters T and R0 satisfy e1(w0)e∫t04b2L2f+1≤R20, we obtain
e(w(t))≤(e1(w0))e∫t04b2L2f+1≤R20. | (3.24) |
Hence, it implies that B maps XT,R0 into itself.
Let us now prove (ⅱ). To demonstrate that B is a contraction mapping with respect to the metric d(.,.) given above, we consider ui∈XT,R0 and wi∈XT,R0, where i=1,2 are the corresponding solutions to (3.21). Let v(t)=(w1−w2)(t), then v satisfies the following system:
vtt+Δ2v−Δv=f(−Δu1)−f(−Δu2), | (3.25) |
with initial conditions
v(0)=0,vt(0)=0, |
and boundary conditions
v=0,∂Δv∂η=−aΔvt. |
Multiplying (3.25) by 2vt, and integrating it over Ω, we find
ddt[‖vt‖22+‖∇v‖22+‖Δv‖22]≤I2+I3, | (3.26) |
where
I2=2b∫Ω(f(−Δu1)−f(−Δu2))vtdx, |
and
I3=2∫ΩΔw2vtdx. |
To proceed the estimates of Ii, i=2,3, we observe that
|I2|≤2b‖f(−Δu1)−f(−Δu2)‖2.‖vt‖2≤2bLf‖Δu1−Δu2‖2.‖vt‖2≤2bLfe(u1−u2)1/2e(v(t))1/2, | (3.27) |
and
|I3|≤‖Δw2‖2.‖vt‖2≤R20e(v(t))1/2. | (3.28) |
Thus, by using (3.27) and (3.28) in (3.26), we get
e(v(t))≤∫t0[2bLfe(u1−u2)1/2e(v(s))1/2+R20e(v(s))1/2]ds. |
So, from Gronwall's inequality, it follows that
e(v(t))≤4b2L2fT2eR20Tsup0≤t≤Te(u1−u2). |
By (3.20), we have
d(w1,w2)≤C(T,R0)1/2d(u1,u2), | (3.29) |
where C(T,R0)=4b2L2fT2eR20T. Hence, under inequality (3.24), B is a contraction mapping if C(T,R0)<1. Indeed, we choose R0 to be sufficiently large and T to be sufficiently small so that (3.24) and (3.29) are simultaneously satisfied. By applying the contraction mapping theorem, we obtain the local existence result.
Remark 3.3. The application of the contraction mapping theorem in Theorem 3.2 guarantees the existence of a unique local solution w(t) defined in the ball B(0,R0)⊂H20(Ω). Since U×(H10(Ω)∩H2(Ω)) is dense in H20(Ω)×L2(Ω), we can obtain the similar priori estimates in Theorem 3.2 for ‖w(t)‖H20(Ω) and this norm remains bounded as t→T∞. So, we can conclude that the solution can be extended to the whole space H20(Ω).
Next, we define a weak solution for the initial and boundary value problem, as follows:
Definition 3.4. A weak solution to the problems (1.1)–(1.3) on (0,T) is any function w∈C(0,T;H20(Ω))∩C(0,T;L2(Ω)), with w0∈H20(Ω) and w1∈L2(Ω) verifying
∫T0∫Ω(−wtϕt+ΔwΔϕ+∇w∇ϕ)dΩdt+∫T0∫Γ(aΔwtϕ)dΓdt=−∫Ω(wtϕ)|T0+b∫T0∫Ωf(−Δw)ϕdΩdt, |
for all test functions ϕ in C(0,T;U)∩C(0,T;L2(Ω)).
In this section, we study the existence of blow-up solutions for the initial and boundary value problems (1.1)–(1.3). We recall the definition for blow-up of the solutions to the problems (1.1)–(1.3).
Definition 4.1. Suppose w is a solution to (1.1)–(1.3) in the maximal existence time interval [0,T∞), 0<T∞≤∞. Then w blows up at T∞ if limsupt→T∞,t<T∞‖w‖2=+∞.
We introduce the energy functional E(t) as:
E(t):=‖∇wt‖22+‖Δw‖22+‖∇Δw‖22−2b⟨F(−Δw),1⟩. | (4.1) |
Furthermore, we define the function ψ(t) as follows:
ψ(t)=‖∇w‖22+∫t0∫Γa(Δw)2dσds+∫Γa(Δw0)2dσ. | (4.2) |
The subsequent lemma demonstrates that our energy functional E(t) defined in (4.1) is a non-increasing function.
Lemma 4.2. Under the assumption (2.1) for the energy function E(t),t>0, the inequality E(t)≤E(0) holds.
Proof. Multiplying Eq (1.1) by −2Δwt in L2(Ω) yields the equality:
−2∫ΩwttΔwtdx+2∫ΩΔwΔwtdx−2∫ΩΔ2wΔwtdx=−2b∫Ωf(−Δw)Δwtdx. | (4.3) |
By using Green's Formula and the boundary conditions (1.2), we obtain
ddt[‖∇wt‖22+‖Δw‖22+‖∇Δw‖22−2b⟨F(−Δw),1⟩]=−2∫Γa(Δwt)2dσ. |
Then, we have,
ddtE(t)=−2∫Γa(Δwt)2dσ. | (4.4) |
It is obvious from (4.4) that E(t)≤E(0) for all t≥0.
Theorem 4.3. Under the assumptions on the parameter of our problem, the functional ψ(t) given by (4.2) satisfies the following inequality:
ψ″(t)ψ(t)−(γ+1)[ψ′(t)]2+d0ψ(t)≥0, |
where
d0:=2(2γ+1)E(0)+2(γ+1)∫Γa(Δw0)2dσ. |
Proof. Differentiating the function ψ defined in Eq (4.2) for t, we obtain
ψ′(t)=2⟨∇w,∇wt⟩+2∫t0∫ΓaΔwΔwtdσds+∫Γa(Δw0)2dσ. | (4.5) |
Taking one more derivative with respect to t and utilizing Green's formula gives:
ψ″(t)=2‖∇wt‖22+2⟨∇w,∇wtt⟩+2a∫ΓΔwΔwtdσ=2‖∇wt‖22−2∫ΩwttΔw+2∫Γ∂w∂ηwttdσ+2a∫ΓΔwΔwtdσ=2‖∇wt‖22−2∫Ω(Δw−Δ2w+bf(−Δw))Δwdx+2a∫ΓΔwΔwtdσ. |
Since
2∫ΩΔwΔ2wdx=2∫Γ∂Δw∂ηΔwdσ−2∫Ω∇(Δw)∇(Δw)dx, |
we obtain,
ψ″(t)=2‖∇wt‖22−2‖Δw‖22−2‖∇Δw‖22+2b⟨f(−Δw),−Δw⟩+2∫Γ∂Δw∂ηΔwdσ+2aΔwΔwtdσ⏟=0. |
By using the inequality (2.1) we have,
ψ″(t)≥2‖∇wt‖22−2‖Δw‖22−2‖∇Δw‖22+4b(2γ+1)⟨F(−Δw),1⟩=−2(2γ+1)E(t)+4(γ+1)‖∇wt‖22+4γ‖Δw‖22+4γ‖∇Δw‖22. | (4.6) |
Thus, we obtain from the inequalities (4.6) and (4.4) that
ψ″(t)≥−2(2γ+1)E(0)+4(2γ+1)∫t0∫Γa(Δwt)2dσds+4(γ+1)‖∇wt‖22+4γ‖Δw‖22+4γ‖∇Δw‖22≥4(γ+1)[‖∇wt‖22+∫t0∫Γa(Δwt)2dσds+12∫Γa(Δw0)2dσ]−d0. |
Multiplying both sides of the following inequality by ψ(t):
ψ″(t)≥4(γ+1)[‖∇wt‖22+∫t0∫Γa(Δwt)2dσds+12∫Γa(Δw0)2dσ]⏟A−d0, |
we get
ψ″(t)ψ(t)≥4(γ+1)Aψ(t)−d0ψ(t). | (4.7) |
From (4.5), we obtain:
(1+γ)[ψ′(t)]2=4(1+γ)[⟨∇w,∇wt⟩+∫t0∫ΓaΔwΔwtdσds+12∫Γa(Δw0)2dσ]2. | (4.8) |
Applying Schwartz's and Hölder's inequalities, we obtain:
(1+γ)[ψ′(t)]2≤4(1+γ)[‖∇w‖2.‖∇wt‖2+{∫t0[∫Γa(Δw)2dσ]ds}12.{∫t0[∫Γa(Δwt)2dσ]ds}12+12∫Γa(Δw0)2dσ]2. | (4.9) |
Now, we introduce the following notations:
X:=‖∇w‖2,X′:={∫t0[∫Γa(Δw)2dσ]ds}12, |
Y:=‖∇wt‖2,Y′:={∫t0[∫Γa(Δwt)2dσ]ds}12,Z:=∫Γa(Δw0)2dσ. |
Hence, from (4.9), we have
4(1+γ)[XY+X′Y′+Z2]2=4(1+γ)[(X2Y2+(X′)2(Y′)2+Z24)+2(XYX′Y′+XYZ2+X′Y′Z2)]. |
By Cauchy's inequality, we obtain
XYZ≤(X22+Y22)ZandX′Y′Z≤((X′)22+(Y′)22)Z. |
On the other hand,
4(1+γ)Aψ(t)=4(1+γ)[Y2+(Y′)2+Z2][X2+(X′)2+Z2]=4(1+γ)[X2Y2+(X′)2Y2+X2(Y′)2+Y2C+(X′)2Y2+(Y′)2C+X2Z2+(X′)2Z2+Z22], |
and we also have
X2(Y′)2+(X′)2Y2=(XY′−X′Y)2+2XX′YY′, |
so, we get
(γ+1)[ψ′(t)]2≤4(γ+1)Aψ(t). | (4.10) |
Consequently, by subtracting (4.10) from (4.7), we obtain,
ψ″(t)ψ(t)−(γ+1)[ψ′(t)]2+d0ψ(t)≥0, |
as desired.
Theorem 4.4. For each fixed w0∈W1,p0(Ω), there exists w1∈L2(Ω) satisfying the conditions
(ψ′(0))2>2β2α−1ψ(0),E(0)>0. | (4.11) |
Hence, by Lemma 2.2 we have the following upper bound for the existence time T0=T0(u0,u1)>0 of the solution:
T0≤ψ1−α(0)A−1,limt↑T∞ψ(t)=+∞forT∞≥T0, |
where
α=1+γ,β=2(2γ+1)E(0)+2(γ+1)∫Γa(Δw0)2dσ, |
and
E(0)=‖∇w1‖22+‖Δw0‖22+‖∇Δw0‖22−2b∫ΓF(Δw0)dx, | (4.12) |
with
ψ(0)=‖∇w0‖22+∫Γa(Δw0)2dσ,ψ′(0)=2⟨∇w0,∇w1⟩+∫Γa(Δw0)2dσ. |
Proof. It is sufficient to prove the resulting conditions in (4.11) are compatible. Firstly, we choose a non-trivial initial function w0(x)∈W1,p0(Ω) in such a way that
∫ΓF(Δw0)dx+4a1/2‖∇w0‖22∫Γ(Δw0)2dσ+a2∫Γ(Δw0)48b‖∇w0‖22+8ba∫Γ(Δw0)2dσ>‖∇w0‖22∫Γ(Δw0)2dσ2b(‖∇w0‖22+∫Γa(Δw0)2+a(1+γ)2b(1+2γ)∫ΓΔw20dσ+‖Δw0‖222b+‖∇Δw0‖222b. | (4.13) |
Fix w0(x) and put w1(x)=λw0(x) with λ>0 so large that the initial energy is guaranteed to be positive:
E(0)=λ2‖∇w0‖22+‖Δw0‖22+‖∇Δw0‖22−2b∫ΓF(Δw0)dx>0. |
Note that ψ′(0)=2λ‖∇w0‖22+∫Γa(Δw0)2>0. Then the condition (4.11) takes the form,
4λ2‖∇w0‖42+4λ‖∇w0‖22∫ΓaΔw20dσ+(∫ΓaΔw20)2>11+2γ(4(1+2γ)E(0)+4(1+γ)∫ΓaΔw20dσ).(‖∇w0‖22+∫ΓaΔw20dσ)=(4E(0)+4(1+γ1+2γ)∫ΓaΔw20dσ)).(‖∇w0‖22+∫ΓaΔw20dσ)=(4λ2‖∇w0‖22+4‖Δw0‖22+4‖∇Δw0‖22−8b∫ΓF(−Δw0)dx+4(1+γ1+2γ)∫ΓaΔw20dσ).(‖∇w0‖22+∫ΓaΔw20dσ)=4λ2‖∇w0‖42+4λ‖∇w0‖22∫ΓaΔw20dσ+(4(1+γ1+2γ)∫ΓaΔw20dσ+4‖Δw0‖22+4‖∇Δw0‖22−8b∫ΓF(−Δw0)dx).(‖∇w0‖22+∫ΓaΔw20dσ). | (4.14) |
Write λ=1/a1/2, where a>0. Then a series of the transformations in (4.14) yields the inequality that coincides with (4.13). This proves that the conditions (4.11) are compatible for sufficiently small a>0.
Remark 4.5. Consider the function f from Assumption (A2) and the functions w0 and w1 that satisfy the following conditions:
(i) By Theorem 4.4, the bounded function ψ defined in Eq (4.2) and its derivative ψ′ satisfy Lemma 2.2.
(ii) Additionally, the initial energy functional E(0) defined in Eq (4.12) is positive.
Therefore, a positive number exists T>0 such as T<T∞, where ψ(t)→+∞ as t→T∞.
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
The authors are grateful to the reviewers for their valuable comments and suggestions.
The authors declare there are no conflicts of interest.
[1] |
A. S. Perelson, P. W. Nelson, Mathematical analysis of HIV-1 dynamics in vivo, SIAM Rev., 41 (1999), 3–44. https://doi.org/10.1137/S0036144598335107 doi: 10.1137/S0036144598335107
![]() |
[2] | M. Nowal, R. M. May, Virus dynamics: mathematical principles of immunology and virology, Oxford University Press, Oxford, 2000. |
[3] |
A. S. Perelson, R. M. Ribeiro, Modeling the within-host dynamics of HIV infection, BMC Biol., 11 (2013), 1–10. https://doi.org/10.1186/1741-7007-11-96 doi: 10.1186/1741-7007-11-96
![]() |
[4] | G. W. Nelson, A. S. Perelson, A mechanism of immune escape by slow-replicating HIV strains, J. Acq. Imm. Def., 5 (1992), 82–93. |
[5] |
A. S. Perelson, D. E. Kirschner, R. D. Boer, Dynamics of HIV infection of CD4+ T cells, Math. Biosci., 114 (1993), 81–125. https://doi.org/10.1016/0025-5564(93)90043-A doi: 10.1016/0025-5564(93)90043-A
![]() |
[6] |
L. Rong, A. S. Perelson, Modeling HIV persistence, the latent reservoir, and viral blips, J. Theor. Biol., 260 (2009), 308–331. https://doi.org/10.1016/j.jtbi.2009.06.011 doi: 10.1016/j.jtbi.2009.06.011
![]() |
[7] |
N. K. Vaidya, R. M. Ribeiro, A. S. Perelson, A. Kumar, Modeling the effects of morphine on simian immunodeficiency virus dynamics, PLoS Comput. Biol., 12 (2016), e1005127. https://doi.org/10.1371/journal.pcbi.1005127 doi: 10.1371/journal.pcbi.1005127
![]() |
[8] |
M. A. Stafford, L. Corey, Y. Cao, E. S. Daar, D. D. Ho, A. S. Perelson, Modeling plasma virus concentration during primary HIV infection, J. Theor. Biol., 203 (2000), 285–301. https://doi.org/10.1006/jtbi.2000.1076 doi: 10.1006/jtbi.2000.1076
![]() |
[9] | A. S. Perelson, P. W. Nelson, Modeling viral infections, in Proceedings of Symposia in Applied Mathematics, 59 (2002), 139–172. |
[10] | R. Patil, U. Raghuwanshi, Serum protein, albumin, globulin levels, and A/G ratio in HIV positive patients, Biomed. Pharmacol. J., 2 (2009), 321–325. |
[11] |
V. T. Sowmyanarayanan, S. Jun, A. Cowan, R. L. Bailey, The nutritional status of HIV-Infected US adults, Curr. Dev. Nutr., 1 (2017), e001636. https://doi.org/10.3945/cdn.117.001636 doi: 10.3945/cdn.117.001636
![]() |
[12] | R. K. Chandra, Nutrition and immunity: Ⅰ. Basic considerations. Ⅱ. Practical applications, ASDC J. Dent. Child., 54 (1987), 193–197. |
[13] | W. R. Beisel, Nutrition in pediatric HIV infection: setting the research agenda, J. Nutr., 126 (1996), 2611–2615. |
[14] |
O. O. Oguntibeju, W. M. Van den Heever, F. E. Van Schalkwyk, The interrelationship between nutrition and the immune system in HIV infection: a review, Pak. J. Biol. Sci., 10 (2007), 4327–4338. https://doi.org/10.3923/pjbs.2007.4327.4338 doi: 10.3923/pjbs.2007.4327.4338
![]() |
[15] |
M. A. Eller, N. Goonetilleke, B. Tassaneetrithep, L. A. Eller, M. C. Costanzo, S. Johnson, et al., Expansion of inefficient HIV-specific CD8 T cells during acute infection, J. Virol., 90 (2016), 4005–4016. https://doi.org/10.1128/jvi.02785-15 doi: 10.1128/jvi.02785-15
![]() |
[16] |
T. Were, J. O. Jesca, E. Munde, C. Ouma, T. M. Titus, F. Ongecha-Owuor, et al., Clinical chemistry profiles in injection heroin users from Coastal Region, Kenya, BMC Clin. Pathol., 14 (2014), 1–9. https://doi.org/10.1186/1472-6890-14-32 doi: 10.1186/1472-6890-14-32
![]() |
[17] |
N. Tuncer, T. T. Le, Structural and practical identifiability analysis of outbreak models, Math. Biosci., 299 (2018), 1–18. https://doi.org/10.1016/j.mbs.2018.02.004 doi: 10.1016/j.mbs.2018.02.004
![]() |
[18] |
N. Tuncer, M. Marctheva, B. LaBarre, S. Payoute, Structural and practical identifiability analysis of Zika epidemiological models, Bull. Math. Biol., 80 (2018), 2209–2241. https://doi.org/10.1007/s11538-018-0453-z doi: 10.1007/s11538-018-0453-z
![]() |
[19] |
N. Tuncer, A. Timsina, M. Nuno, G. Chowell, M. Martcheva, Parameter identifiability and optimal control of an SARS-CoV-2 model early in the pandemic, J. Biol. Dyn., 16 (2022), 412–438. https://doi.org/10.1080/17513758.2022.2078899 doi: 10.1080/17513758.2022.2078899
![]() |
[20] |
H. Miao, X. Xia, A. S. Perelson, H. Wu, On the identifiability of nonlinear ODE models and applications in viral dynamics, SIAM Rev., 53 (2011), 3–39. https://doi.org/10.1137/090757009 doi: 10.1137/090757009
![]() |
[21] |
E. A. Dankwa, A. F. Brouwer, C. A. Donnelly, Structural identifiability of compartmental models for infectious disease transmission is influenced by data type, Epidemics, 41 (2022), 100643. https://doi.org/10.1016/j.epidem.2022.100643 doi: 10.1016/j.epidem.2022.100643
![]() |
[22] |
G. Massonis, J. R. Banga, A. F. Villaverde, Structural identifiability and observability of compartmental models of the COVID-19 pandemic, Annu. Rev. Control, 51 (2021), 441–459. https://doi.org/10.1016/j.arcontrol.2020.12.001 doi: 10.1016/j.arcontrol.2020.12.001
![]() |
[23] |
M. Renardy, D. Kirschne, M. Eisenberg, Structural identifiability analysis of age-structured PDE epidemic models, J. Math. Biol., 84 (2022). https://doi.org/10.1007/s00285-021-01711-1 doi: 10.1007/s00285-021-01711-1
![]() |
[24] |
L. Gallo, M. Frasca, V. Latora, G. Russo, Lack of practical identifiability may hamper reliable predictions in COVID-19 epidemic models, Sci. Adv., 8 (2022), eabg5234. https://doi.org/10.1126/sciadv.abg5234 doi: 10.1126/sciadv.abg5234
![]() |
[25] |
K. Roosa, G. Chowell, Assessing parameter identifiability in compartmental dynamic models using a computational approach: application to infectious disease transmission models, Theor. Biol. Med. Model., 16 (2019). https://doi.org/10.1186/s12976-018-0097-6 doi: 10.1186/s12976-018-0097-6
![]() |
[26] |
C. Tönsing, J. Timmer, C. Kreutz, Profile likelihood-based analyses of infectious disease models, Stat. Methods Med. Res., 27 (2018), 1979–1998. https://doi.org/10.1177/0962280217746444 doi: 10.1177/0962280217746444
![]() |
[27] |
N. Heitzman-Breen, Y. R. Liyanage, N. Duggal, N. Tuncer, S. M. Ciupe, The effect of model structure and data availability on Usutu virus dynamics at three biological scales, Roy. Soc. Open Sci., 11 (2024), 231146. https://doi.org/10.1098/rsos.231146 doi: 10.1098/rsos.231146
![]() |
[28] |
V. Sreejithkumar, K. Ghods, T. Bandara, M. Martcheva, N. Tuncer, Modeling the interplay between albumin-globulin metabolism and HIV infection, Math. Biosci. Eng., 20 (2023), 19527–19552. https://doi.org/10.1098/rsos.231146 doi: 10.1098/rsos.231146
![]() |
[29] |
N. Tuncer, M. Martcheva, Determining reliable parameter estimates for within-host and within-vector models of Zika virus, J. Biol. Dyn., 15 (2021), 430–454. https://doi.org/10.1080/17513758.2021.1970261 doi: 10.1080/17513758.2021.1970261
![]() |
[30] |
N. Tuncer, M. Martcheva, B. LaBarre, S. Payoute, Structural and practical identifiability analysis of Zika epidemiological models, Bull. Math. Biol., 80 (2018), 2209–2241. https://doi.org/10.1007/s11538-018-0453-z doi: 10.1007/s11538-018-0453-z
![]() |
[31] |
N. Tuncer, H. Gulbudak, V. L. Cannataro, M. Martcheva, Structural and practical identifiability issues of immuno-epidemiological vector–host models with application to rift valley fever, Bull. Math. Biol., 78 (2016), 1796–1827. https://doi.org/10.1007/s11538-016-0200-2 doi: 10.1007/s11538-016-0200-2
![]() |
[32] |
S. M. Ciupe, N. Tuncer, Identifiability of parameters in mathematical models of SARS-CoV-2 infections in humans, Sci. Rep., 12 (2022), 14637. https://doi.org/10.1038/s41598-022-18683-x doi: 10.1038/s41598-022-18683-x
![]() |
[33] |
M. C. Eisenberg, S. L. Robertson, J. H. Tien, Identifiability and estimation of multiple transmission pathways in Cholera and waterborne disease, J. Theor. Biol., 324 (2013), 84–102. https://doi.org/10.1016/j.jtbi.2012.12.021 doi: 10.1016/j.jtbi.2012.12.021
![]() |
[34] |
G. Bellu, M. P. Saccomani, S. Audoly, L. D'Angiò, DAISY: A new software tool to test global identifiability of biological and physiological systems, Comput. Meth. Prog. Bio., 88 (2007), 52–61. https://doi.org/10.1016/j.cmpb.2007.07.002 doi: 10.1016/j.cmpb.2007.07.002
![]() |
[35] |
H. Miao, C. Dykes, L. M. Demeter, J. Cavenaugh, S. Y. Park, A. S. Perelson, et al., Modeling and estimation of kinetic parameters and replicative fitness of HIV-1 from flow-cytometry-based growth competition experiment, Bull. Math. Biol., 70 (2008), 1749–1771. https://doi.org/10.1007/s11538-008-9323-4 doi: 10.1007/s11538-008-9323-4
![]() |
[36] |
H. Wu, H. Zhu, H. Miao, A. S. Perelson, Parameter identifiability and estimation of HIV/AIDS dynamic models, B. Math. Biol., 70 (2008), 785–799. https://doi.org/10.1007/s11538-007-9279-9 doi: 10.1007/s11538-007-9279-9
![]() |
[37] |
F. G. Wieland, A. L. Hauber, M. Rosenblatt, C. Tonsing, J. Timmer, On structural and practical identifiability, Curr. Opin Syst. Biol., 25 (2021), 60–69. https://doi.org/10.1016/j.coisb.2021.03.005 doi: 10.1016/j.coisb.2021.03.005
![]() |
[38] |
A. Pironet, P. D. Docherty, P. C. Dauby, J. G. Chase, T. Desaive, Practical identifiability analysis of a minimal cardiovascular system model, Comput. Meth. Prog. Bio., 171 (2019), 53–65. https://doi.org/10.1016/j.cmpb.2017.01.005 doi: 10.1016/j.cmpb.2017.01.005
![]() |
[39] |
A. Raue, J. Karlsson, M. P. Saccomani, M. Jirstrand, J. Timmer, Comparison of approaches for parameter identifiability analysis of biological systems, Bioinformatics, 30 (2014), 1440–1448. https://doi.org/10.1093/bioinformatics/btu006 doi: 10.1093/bioinformatics/btu006
![]() |
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