Alkaptonuria (AKU) is a rare metabolic disease which is inherited as an autosomal recessive trait. It is characterized by the accumulation of homogentisic acid over time in various tissues of the body particularly connective tissues. This genetic disease is caused by mutation of the Homogentisate 1,2-dioxygenase (HGD) gene which encodes for enzyme essential for the catabolism of phenylalanine and tyrosine. The aim of the present study is to investigate variant types in Jordanian patients with alkaptonuria. Genomic DNA was extracted from whole blood samples of the participated AKU family members (n = 23). The 14 exons of HGD gene for the proband were amplified using specific PCR primers. The sequenced data were analysed and the pathogenicity of the identified variants were predicted using the online bioinformatics programs: PolyPhen2, SIFT and Mutation taster. The analysis showed that the proband was compound heterozygous for the missense mutations A122V and R225C found within E6 and E10, respectively. R225C variant is novel and the genotyping of the family members indicated that HGDA122V and HGDR225C alleles were fully segregated. Moreover, the cousins of the proband who are AKU patients inherited the homozygous pattern of the novel mutation. This study extends the pathogenic mutations spectrum of the HGD gene. It identified the novel mutation R225C and at the same time confirmed the high prevalence of the founder mutation A122V in Jordanian AKU patients.
Citation: Nesrin R. Mwafi, Dema A. Ali, Raida W. Khalil, Ibrahim N. Alsbou', Ahmad M. Saraireh. Novel R225C variant identified in the HGD gene in Jordanian patients with alkaptonuria[J]. AIMS Molecular Science, 2021, 8(1): 60-75. doi: 10.3934/molsci.2021005
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Alkaptonuria (AKU) is a rare metabolic disease which is inherited as an autosomal recessive trait. It is characterized by the accumulation of homogentisic acid over time in various tissues of the body particularly connective tissues. This genetic disease is caused by mutation of the Homogentisate 1,2-dioxygenase (HGD) gene which encodes for enzyme essential for the catabolism of phenylalanine and tyrosine. The aim of the present study is to investigate variant types in Jordanian patients with alkaptonuria. Genomic DNA was extracted from whole blood samples of the participated AKU family members (n = 23). The 14 exons of HGD gene for the proband were amplified using specific PCR primers. The sequenced data were analysed and the pathogenicity of the identified variants were predicted using the online bioinformatics programs: PolyPhen2, SIFT and Mutation taster. The analysis showed that the proband was compound heterozygous for the missense mutations A122V and R225C found within E6 and E10, respectively. R225C variant is novel and the genotyping of the family members indicated that HGDA122V and HGDR225C alleles were fully segregated. Moreover, the cousins of the proband who are AKU patients inherited the homozygous pattern of the novel mutation. This study extends the pathogenic mutations spectrum of the HGD gene. It identified the novel mutation R225C and at the same time confirmed the high prevalence of the founder mutation A122V in Jordanian AKU patients.
Alkaptonuria;
Gas Chromatography-Mass Spectrometry analysis;
multiplex ligation-dependent probe amplification
In this paper, we consider the 3D nonlinear damped micropolar equation
{ut+(u⋅∇)u−(ν+κ)Δu+σ|u|β−1u+∇p=2κ∇×ω+f1(x,t),ωt+(u⋅∇)ω+4κω−γΔω−μ∇∇⋅ω=2κ∇×u+f2(x,t),∇⋅u=0,u(x,t)|t=τ=uτ(x), ω(x,t)|t=τ=ωτ(x), | (1.1) |
where (x,t)∈Ω×[τ,+∞), τ∈R, Ω⊆R3 is a bounded domain, u=u(x,t) is the fluid velocity, ω=ω(x,t) is the angular velocity, σ is the damping coefficient, which is a positive constant, f1=f1(x,t) and f2=f2(x,t) represent external forces, ν, κ, γ, μ are all positive constants, γ and μ represent the angular viscosities.
Micropolar flow can describe a fluid with microstructure, that is, a fluid composed of randomly oriented particles suspended in a viscous medium without considering the deformation of fluid particles. Since Eringen first published his paper on the model equation of micropolar fluids in 1966 [5], the formation of modern theory of micropolar fluid dynamics has experienced more than 40 years of development. For the 2D case, many researchers have discussed the long time behavior of micropolar equations (such as [2,4,10,24]). It should be mentioned that some conclusions in the 2D case no longer hold for the 3D case due to different structures of the system. In the 3D case, the work of micropolar equations (1.1) with σ=0, f1=0, and f2=0 has attracted a lot of attention (see [6,14,19]). Galdi and Rionero [6] proved the existence and uniqueness of solutions of 3D incompressible micropolar equations. In a 3D bounded domain, for small initial data Yamaguchi [19] investigated the existence of a global solution to the initial boundary problem for the micropolar system. In [14], Silva and Cruz et al. studied the L2-decay of weak solutions for 3D micropolar equations in the whole space R3. When f1=f2=0, for the Cauchy problem of the 3D incompressible nonlinear damped micropolar equations, Ye [22] discussed the existence and uniqueness of global strong solutions when β=3 and 4σ(ν+κ)>1 or β>3. In [18], Wang and Long showed that strong solutions exist globally for any 1≤β≤3 when initial data satisfies some certain conditions. Based on [22], Yang and Liu [20] obtained uniform estimates of the solutions for 3D incompressible micropolar equations with damping, and then they proved the existence of global attractors for 3<β<5. In [7], Li and Xiao investigated the large time decay of the L2-norm of weak solutions when β>145, and considered the upper bounds of the derivatives of the strong solution when β>3. In [21], for 1≤β<73, Yang, Liu, and Sun proved the existence of trajectory attractors for 3D nonlinear damped micropolar fluids.
To the best of our knowledge, there are few results on uniform attractors for the three-dimensional micropolar equation with nonlinear damping term. The purpose of this paper is to consider the existence of uniform attractors of system (1.1). When ω=0,κ=0, system (1.1) is reduced to the Navier-Stokes equations with damping. In recent years, some scholars have studied the three-dimensional nonlinear damped Navier-Stokes equations (see [1,13,15,16,23,25]). In order to obtain the desired conclusion, we will use some proof techniques which have been used in the 3D nonlinear damped Navier Stokes equations. Note that, in [20], for the convenience of discussion the authors choose κ,μ=12,γ=1, and ν=32. In this work, we do not specify these parameters, but only require them to be positive real numbers. More importantly, we obtain the existence of uniform attractors in the case of β>3, which undoubtedly expands the range of β when the global attractor exists in [20], i.e., 3<β<5. For the convenience of discussion, similar to [3,8,9,11,16], we make some translational compactness assumption on the external forces term in this paper.
The organizational structure of this article is as follows: In Section 2, we give some basic definitions and properties of function spaces and process theory which will be used in this paper. In Section 3, using various Sobolev inequalities and Gronwall inequalities, we make some uniform estimates from the space with low regularity to high regularity on the solution of the equation. Based on these uniform estimates, in Section 4 we prove that the family of processes {U(f1,f2)(t,τ)}t≥τ corresponding to (1.1) has uniform attractors A1 in V1×V2 and A2 in H2(Ω)×H2(Ω), respectively. Furthermore, we prove A1=A2.
We define the usual functional spaces as follows:
V1={u∈(C∞0(Ω))3:divu=0,∫Ωudx=0},V2={ω∈(C∞0(Ω))3:∫Ωωdx=0},H1=the closure of V1 in (L2(Ω))3,H2=the closure of V2 in (L2(Ω))3,V1=the closure of V1 in (H1(Ω))3,V2=the closure of V2 in (H1(Ω))3. |
For H1 and H2 we have the inner product
(u,υ)=∫Ωu⋅υdx, ∀u,v∈H1,or u,v∈H2, |
and norm ‖⋅‖2=‖⋅‖22=(⋅,⋅). In this paper, Lp(Ω)=(Lp(Ω))3, and ‖⋅‖p represents the norm in Lp(Ω).
We define operators
Au=−PΔu=−Δu, Aω=−Δω, ∀(u,ω)∈H2×H2,B(u)=B(u,u)=P((u⋅∇)u), B(u,ω)=(u⋅∇)ω, ∀(u,ω)∈V1×V2,b(u,υ,ω)=⟨B(u,υ),ω⟩=3∑i,j=1∫Ωui(Diυj)ωjdx, ∀u∈V1,υ,ω∈V2, |
where P is the orthogonal projection from L2(Ω) onto H1. Hs(Ω)=(Hs(Ω))3 is the usual Sobolev space, and its norm is defined by ∥⋅∥Hs=∥As2⋅∥; as s=2, ∥⋅∥H2=∥A⋅∥.
Let us rewrite system (1.1) as
{ut+B(u)+(ν+κ)Au+G(u)=2κ∇×ω+f1(x,t),ωt+B(u,ω)+4κω+γAω−μ∇∇⋅ω=2κ∇×u+f2(x,t),∇⋅u=0,u(x,t)|t=τ=uτ(x), ω(x,t)|t=τ=ωτ(x), | (2.1) |
where we let G(u)=P(σ|u|β−1u).
The Poincarˊe inequality [17] gives
√λ1‖u‖≤‖∇u‖,√λ2‖ω‖≤‖∇ω‖,∀(u,ω)∈V1×V2, | (2.2) |
√λ1∥∇u∥≤∥Au∥, √λ2∥∇ω∥≤∥Aω∥,∀(u,ω)∈H2(Ω)×H2(Ω), | (2.3) |
where λ1 is the first eigenvalue of Au, and λ2 is the first eigenvalue of Aω. Let λ=min{λ1,λ2}. Then, we have
λ(‖u‖2+‖ω‖2)≤‖∇u‖2+‖∇ω‖2, ∀(u,ω)∈V1×V2,λ(‖∇u‖2+‖∇ω‖2)≤‖Au‖2+‖Aω‖2,∀(u,ω)∈H2(Ω)×H2(Ω). |
Agmon's inequality [17] gives
∥u∥∞≤d1∥∇u∥12∥Δu∥12, ∀u∈H2(Ω). |
The trilinear inequalities [12] give
|b(u,v,w)|≤∥u∥∞∥∇v∥∥w∥,∀u∈L∞(Ω),v∈V1 or V2,w∈H1 or H2, | (2.4) |
|b(u,v,w)|≤k∥u∥14∥∇u∥34∥∇v∥∥w∥14∥∇w∥34,∀u,v,w∈V1 or V2, | (2.5) |
|b(u,v,w)|≤k∥∇u∥∥∇v∥12∥Av∥12∥w∥,∀u∈V1 or V2,v∈H2,w∈H1 or H2. | (2.6) |
Recall that a function f(t) is translation bounded (tr.b.) in L2loc(R;L2(Ω)) if
∥f∥2L2b=∥f∥2L2b(R;L2(Ω))=supt∈R∫t+1t∥f(t)∥2dt<∞, |
where L2b(R;L2(Ω)) represents the collection of functions that are tr.b. in L2loc(R;L2(Ω)). We say that H(f0)=¯{f0(⋅+t):t∈R} is the shell of f0 in L2loc(R;L2(Ω)). If H(f0) is compact in L2loc(R;L2(Ω)), then we say that f0(x,t)∈L2loc(R;L2(Ω)) is translation compact (tr.c.). We use L2c(R;L2(Ω)) to express the collection of all translation compact functions in L2loc(R;L2(Ω)).
Next, we will provide the existence and uniqueness theorems of the solution of Eq (2.1).
Definition 2.1. A function pair (u,ω) is said to be a global strong solution to system (2.1) if it satisfies
(u,ω)∈L∞(τ,T;V1×V2)∩L2(τ,T;H2(Ω)×H2(Ω)), |
|u|β−12∇u∈L2(τ,T;L2(Ω)), ∇|u|β+12∈L2(τ,T;L2(Ω)), |
for any given T>τ.
Theorem 2.1. Suppose (uτ,ωτ)∈V1×V2 with ∇⋅uτ=0,f1,f2∈L2b(R;L2(Ω)). If β=3 and 4σ(ν+κ)>1 or β>3, then there exists a unique global strong solution of (2.1).
Proof. Since the proof method is similar to that of Theorem 1.2 in [22], we omit it here.
Let Σ be a metric space. X, Y are two Banach spaces, and Y⊂X is continuous. {Uσ(t,τ)}t≥τ, σ∈Σ is a family of processes in Banach space X, i.e., u(t)=Uσ(t,τ)uτ, Uσ(t,s)Uσ(s,τ)=Uσ(t,τ),∀t≥s≥τ,τ∈R,Uσ(τ,τ)=I, where σ∈Σ is a time symbol space. B(X) is the set of all bounded subsets of X. Rτ=[τ,+∞).
For the basic concepts of bi-space uniform absorbing set, uniform attracting set, uniform attractor, uniform compact, and uniform asymptotically compact of the family of processed {Uσ(t,τ)}t≥τ,σ∈Σ, one can refer to [9,16].
Let T(h) be a family of operators acting on Σ, satisfying: T(h)σ(s)=σ(s+h),∀s∈R. In this paper, we assume that Σ satisfies
(C1) T(h)Σ=Σ, ∀h∈R+;
(C2) translation identity:
Uσ(t+h,τ+h)=UT(h)σ(t,τ), ∀σ∈Σ,t≥τ,τ∈R,h≥0. |
Theorem 2.2. [3] If the family of processes {Uσ(t,τ)}t≥τ,σ∈Σ is (X,Y)-uniformly (w.r.t. σ∈Σ) asymptotically compact, then it has a (X,Y)-uniform (w.r.t. σ∈Σ) attractor AΣ, AΣ is compact in Y, and it attracts all bounded subsets of X in the topology of Y.
In this paper, the letter C represents a positive constant. It may represent different values in different lines, or even in the same line.
In this paper, we chose H(f01)×H(f02) as the symbol space. Obviously, T(t)(H((f01)×H(f02))=H(f01)×H(f02), for all t≥0. {T(t)}t≥0 is defined by
T(h)(f1(⋅),f2(⋅))=(f1(⋅+h),f2(⋅+h)), ∀h≥0,(f1,f2)∈H(f01)×H(f02), |
which is a translation semigroup and is continuous on H(f01)×H(f02).
Thanks to Theorem 2.1, when (uτ,ωτ)∈V1×V2, f1,f2∈L2loc(R;L2(Ω)), and β>3, we can define a process {U(f1,f2)(t,τ)}t≥τ in V1×V2 by
U(f1,f2)(t,τ)(uτ,ωτ)=(u(t),ω(t)), t≥τ, |
where (u(t),ω(t)) is the solution of Eq (1.1) with external forces f1,f2 and initial data (uτ,ωτ).
Next, let us assume that the external forces f01(x,t),f02(x,t) are tr.c. in L2loc(R;L2(Ω)). Then, f01,f02 are tr.b. in L2loc(R;L2(Ω)), and
∥f1∥2L2b=∥f1∥2L2b(R;L2(Ω))=supt∈R∫t+1t∥f1(s)∥2ds≤∥f01∥2L2b<+∞,∀f1∈H(f01), |
∥f2∥2L2b=∥f2∥2L2b(R;L2(Ω))=supt∈R∫t+1t∥f2(s)∥2ds≤∥f02∥2L2b<+∞,∀f2∈H(f02). |
Furthermore, we assume f01,f02 are uniformly bounded in L2(Ω), i.e., there exists a positive constant K, which satisfies
supt∈R∥f01(x,t)∥≤K, supt∈R∥f02(x,t)∥≤K. |
Meanwhile, we suppose the derivatives df01dt, df02dt, labeled as h1,h2, also belong to L2c(R;L2(Ω)).
Lemma 3.1. Suppose (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). If β>3 then there exists a time t0 and constants ρ1,I1 such that, for any t≥t0,
‖u(t)‖2+‖ω(t)‖2≤ρ1, | (3.1) |
∫t+1t[‖∇u(s)‖2+‖∇ω(s)‖2+‖u(s)‖β+1β+1+‖∇⋅ω(s)‖2]ds≤I1. | (3.2) |
Proof. Multiplying (1.1)1 and (1.1)2 with external forces f1∈H(f01), f2∈H(f02) by u and ω, respectively, and integrating the results equations on Ω, using H¨older's inequality, Young's inequality, and Poincarˊe's inequality, it yields
12ddt(‖u(t)‖2+‖ω(t)‖2)+(ν+κ)‖∇u‖2+γ‖∇ω‖2+4κ‖ω(t)‖2+σ‖u(t)‖β+1β+1+μ‖∇⋅ω‖2=4κ∫Ω∇×u⋅ωdx+(f1,u(t))+(f2,ω(t))≤κ∥∇u∥2+4κ∥ω∥2+νλ2∥u∥2+γλ2∥ω∥2+12νλ∥f1∥2+12γλ∥f2∥2≤(ν2+κ)‖∇u‖2+γ2‖∇ω‖2+4κ‖ω(t)‖2+12νλ∥f1∥2+12γλ∥f2∥2. | (3.3) |
So, we can obtain that
ddt(‖u(t)‖2+‖ω(t)‖2)+ν‖∇u‖2+γ‖∇ω‖2+2σ‖u(t)‖β+1β+1+2μ‖∇⋅ω‖2≤1νλ‖f1(t)‖2+1γλ‖f2(t)‖2, | (3.4) |
and by Poincarˊe's inequality, it yields
ddt(‖u(t)‖2+‖ω(t)‖2)+λα(‖u(t)‖2+‖ω(t)‖2)≤1λα(‖f1(t)‖2+‖f2(t)‖2), | (3.5) |
where α=min{ν,γ}. So, by Gronwall's inequality, we get
‖u(t)‖2+‖ω(t)‖2≤(‖uτ‖2+‖ωτ‖2)e−λα(t−τ)+1λα∫tτe−λα(t−s)(‖f1(s)‖2+‖f2(s)‖2)ds≤(‖uτ‖2+‖ωτ‖2)e−λα(t−τ)+1λα[∫tt−1e−λα(t−s)(‖f1(s)‖2+‖f2(s)‖2)ds+∫t−1t−2e−λα(t−s)(‖f1(s)‖2+‖f2(s)‖2)ds+...]≤(‖uτ‖2+‖ωτ‖2)e−λα(t−τ)+1λα[1+e−λα+e−2λα+...](‖f1‖2L2b+‖f2‖2L2b)≤(‖uτ‖2+‖ωτ‖2)e−λα(t−τ)+1λα(1−e−λα)−1(‖f1‖2L2b+‖f2‖2L2b)≤(‖uτ‖2+‖ωτ‖2)e−λα(t−τ)+1λα(1+1λα)(‖f1‖2L2b+‖f2‖2L2b), ∀t≥τ. |
Therefore, there must exists a time t0≥τ+1λαlnλ2α2(‖uτ‖2+‖ωτ‖2)(1+λα)(‖f1‖2L2b+‖f2‖2L2b), such that, ∀t≥t0,
‖u(t)‖2+‖ω(t)‖2≤2λα(1+1λα)(‖f1‖2L2b+‖f2‖2L2b)≡ρ1. | (3.6) |
Taking t≥t0, integrating (3.4) from t to t+1, and noticing (3.6), we get
∫t+1t[ν‖∇u(s)‖2+γ‖∇ω(s)‖2+2σ‖u(s)‖β+1β+1+2μ‖∇⋅ω(s)‖2]ds≤(‖u(t)‖2+‖ω(t)‖2)+1νλ∫t+1t‖f1(s)‖2ds+1γλ∫t+1t‖f2(s)‖2ds≤ρ1+1λα(‖f1‖2L2b+‖f2‖2L2b), ∀t≥t0. | (3.7) |
Letting δ1=min{ν,γ,2σ,2μ}, we have
δ1∫t+1t[‖∇u(s)‖2+‖∇ω(s)‖2+‖u(s)‖β+1β+1+‖∇⋅ω(s)‖2]ds≤ρ1+1λα(‖f1‖2L2b+‖f2‖2L2b), ∀t≥t0. |
Letting I1=1δ1(ρ1+1λα(‖f1‖2L2b+‖f2‖2L2b)), we have
∫t+1t[‖∇u(s)‖2+‖∇ω(s)‖2+‖u(s)‖β+1β+1+‖∇⋅ω(s)‖2]ds≤I1, ∀t≥t0. |
This completes the proof of Lemma 3.1.
Lemma 3.2. Assume β>3, (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). Then, there exists a time t2 and a constant ρ2 such that
‖∇u(t)‖2+‖∇ω(t)‖2+∫t+1t(‖Au(s)‖2+‖Aω(s)‖2+‖|u|β−12∇u‖2+‖∇|u|β+12‖2)ds≤ρ2, | (3.8) |
for any t≥t2.
Proof. Taking the inner product of −Δu in H1 with the first equation of (1.1), we obtain
12ddt‖∇u‖2+(ν+κ)‖Au‖2+σ‖|u|β−12∇u‖2+4σ(β−1)(β+1)2‖∇|u|β+12‖2=−b(u,u,Au)+2κ∫Ω∇×ω⋅Audx+(f1(t),Au). | (3.9) |
In [18], we find that, when β>3,
∫Ω(u⋅∇u)⋅Δudx≤ν+κ4∥Δu∥2+σ2∥|u|β−12∇u∥2+C1∥∇u∥2, | (3.10) |
where C1=N2ν+κ+N2(ν+κ)(Nβ−1+1), and N is sufficiently large such that
N≥(2β−3)1β−1 and N2(ν+κ)(Nβ−1+1)≤σ2. |
And, because
|2κ∫Ω∇×ω⋅Audx|≤ν+κ4∥Δu∥2+4κ2ν+κ∥∇ω∥2, | (3.11) |
|(f1(t),Au)|≤ν+κ4∥Δu∥2+∥f1(t)∥2ν+κ, | (3.12) |
so combining (3.10)–(3.12) with (3.9), we have
ddt‖∇u‖2+ν+κ2‖Au‖2+σ‖|u|β−12∇u‖2+8σ(β−1)(β+1)2‖∇|u|β+12‖2≤2C1‖∇u‖2+8κ2ν+κ∥∇ω∥2+2∥f1(t)∥2ν+κ≤C2(‖∇u‖2+‖∇ω‖2+‖f1(t)‖2), | (3.13) |
where C2=max{2C1,8κ2ν+κ,2ν+κ}.
Applying uniform Gronwall's inequality to (3.13), we obtaint, ∀t≥t0+1≡t1,
‖∇u(t)‖2+∫t+1t(ν+κ2‖Au(s)‖2+σ‖|u(s)|β−12∇u(s)‖2+8σ(β−1)(β+1)2‖∇|u(s)|β+12‖2)ds≤C3, | (3.14) |
where C3 is a positive constant dependent on C2, I1, and ∥f01∥2L2b.
Taking the inner product of −Δω in H2 with the second equation of (1.1), we get
12ddt‖∇ω‖2+4κ‖∇ω‖2+γ‖Aω‖2+μ‖∇∇⋅ω‖2=−b(u,ω,Aω)+2κ∫Ω∇×u⋅Aωdx+(f2(t),Aω)≤3γ4‖Aω‖2+d21γ‖∇u‖‖Au‖‖∇ω‖2+4κ2γ‖∇u‖2+1γ‖f2(t)‖2. | (3.15) |
In the last inequality of (3.15), we used Agmon's inequality and the trilinear inequality. Then,
ddt‖∇ω‖2+γ2‖Aω‖2+2μ‖∇∇⋅ω‖2≤C4(‖∇u‖‖Au‖‖∇ω‖2+‖∇u‖2+‖f2(t)‖2), | (3.16) |
where C4=max{2d21γ,8κ2γ,2γ}.
By the uniform Gronwall's inequality, we easily obtain that, for t≥t1+1≡t2,
‖∇ω(t)‖2+∫t+1t(γ2‖Aω(s)‖2+2μ‖∇∇⋅ω(s)‖2)ds≤C5, for t≥t1+1≡t2, | (3.17) |
where C5 is a positive constant dependent on C3,C4, and ∥f02∥2L2b.
Adding (3.14) with (3.17) yields
‖∇u(s)‖2+‖∇ω(s)‖2+∫t+1t(‖Au(s)‖2+‖Aω(s)‖2+‖|u(s)|β−12∇u(s)‖2+‖∇|u(s)|β+12‖2)ds≤C, |
for t≥t2. Hence, Lemma 3.2 is proved.
Lemma 3.3. Suppose that (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). Then, for β>3, there exists a time t3 and a constant ρ3 such that
‖u(t)‖β+1+‖∇⋅ω(t)‖2≤ρ3, | (3.18) |
for any t≥t3.
Proof. Multiplying (1.1)1 by ut, then integrating the equation over Ω, we have
‖ut‖2+ν+κ2ddt‖∇u‖2+σβ+1ddt‖u(t)‖β+1β+1=−b(u,u,ut)+2κ∫Ω∇×ω⋅utdx+(f1(t),ut)≤12‖ut‖2+3d212√λ1∥∇u∥2∥Au∥2+6κ2‖∇ω‖2+32‖f1(t)‖2. | (3.19) |
The trilinear inequality (2.4), Agmon's inequality, and Poincarˊe's inequality are used in the last inequality of (3.19).
Hence,
(ν+κ)ddt‖∇u‖2+2σβ+1ddt‖u(t)‖β+1β+1≤C6(∥∇u∥2∥Au∥2+‖∇ω‖2+‖f1(t)‖2), | (3.20) |
where C6=max{3d21√λ1,12κ2,3}.
By (3.20), using Lemmas 3.1 and 3.2 and the uniform Gronwall's inequality, we have
‖u(t)‖β+1≤C, ∀t≥t2+1≡t3. | (3.21) |
Similar to (3.19), multiplying (1.1)2 by ωt and integrating it over Ω, we get
‖ωt‖2+2κddt‖ω‖2+γ2ddt‖∇ω‖2+μ2ddt‖∇⋅ω‖2=−b(u,ω,ωt)+2κ∫Ω∇×u⋅ωtdx+(f2(t),ωt)≤12‖ωt‖2+3d212√λ1∥Au∥2∥∇ω∥2+6κ2‖∇u‖2+32‖f2(t)‖2. | (3.22) |
Hence,
4κddt∥ω∥2+γddt∥∇ω∥2+μddt∥∇⋅ω∥2≤C6(∥Au∥2∥∇ω∥2+∥∇u∥2+∥f2(t)∥2). | (3.23) |
By (3.23), using Lemma 3.2 and the uniform Gronwall's inequality, we infer that
‖∇⋅ω(t)‖2≤C, ∀t≥t3. | (3.24) |
The proof of Lemma 3.3 is finished.
Lemma 3.4. Suppose (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). If β>3, then there exists a time t4 and a constant ρ5, such that
‖ut(s)‖2+‖ωt(s)‖2≤ρ5, | (3.25) |
for any s≥t4.
Proof. Taking the inner products of ut and ωt with the first and second equations of (1.1), respectively, and using (3.19) and (3.22), we find
‖ut‖2+‖ωt‖2+ν+κ2ddt‖∇u‖2+γ2ddt‖∇ω‖2+2κddt‖ω(t)‖2+σβ+1ddt‖u(t)‖β+1β+1+μ2ddt‖∇⋅ω‖2=−b(u,u,ut)−b(u,ω,ωt)+2κ∫Ω∇×ω⋅utdx+2κ∫Ω∇×u⋅ωtdx+(f1(t),ut)+(f2(t),ωt)≤12(‖ut‖2+‖ωt‖2)+C7(‖f1(t)‖2+‖f2(t)‖2+‖∇u‖2+‖∇ω‖2+∥∇u∥2∥Au∥2+∥∇ω∥2∥Au∥2), | (3.26) |
where C7=max{3d212√λ1,6κ2,32}. The trilinear inequality (2.4), Agmon's inequality, and Poincarˊe's inequality are used in the last inequality of (3.26).
Integrating (3.26) over [t,t+1] and using Lemmas 3.1–3.3, we get
∫t+1t(‖ut(s)‖2+‖ωt(s)‖2)ds≤ρ4, ∀t≥t3, | (3.27) |
where ρ4 is a positive constant dependent on C7,ρ2,ρ3, ∥f01∥2L2b, and ∥f02∥2L2b.
We now differentiate (2.1)1 with respect to t, then take the inner product of ut with the resulting equation to obtain
12ddt∥ut∥2+(ν+κ)∥∇ut∥2=−b(ut,u,ut)−∫ΩG′(u)ut⋅utdx+2κ∫Ω∇×ωt⋅utdx+(f1t,ut). | (3.28) |
Then, we differentiate (2.1)2 with respect to t and take the inner product with ωt to obtain
12ddt∥ωt∥2+4κ∥ωt∥2+γ∥∇ωt∥2+μ∥∇⋅ωt∥2=−b(ut,ω,ωt)+2κ∫Ω∇×ut⋅ωtdx+(f2t,ωt). | (3.29) |
Adding (3.28) with (3.29), we have
12ddt(‖ut‖2+‖ωt‖2)+(ν+κ)‖∇ut‖2+γ‖∇ωt‖2+4κ‖ωt‖2+μ‖∇⋅ωt‖2≤|b(ut,u,ut)|+|b(ut,ω,ωt)|+2κ∫Ω∇×ωt⋅utdx+2κ∫Ω∇×ut⋅ωtdx+(f1t,ut)+(f2t,ωt)−∫ΩG′(u)ut⋅utdx:=7∑i=1Li. | (3.30) |
From Lemma 2.4 in [15], we know that G′(u) is positive definite, so
L7=−∫ΩG′(u)ut⋅utdx≤0. | (3.31) |
For L1, using the trilinear inequality (2.5) and Lemma 3.2, we have
L1≤k‖ut‖12‖∇ut‖32‖∇u‖≤ν+κ4‖∇ut‖2+C‖ut‖2‖∇u‖4≤ν+κ4‖∇ut‖2+C‖ut‖2, for t≥t2. | (3.32) |
For L2, by H¨older's inequality, Gagliardo-Nirenberg's inequality, and Young's inequality, we have
L2≤C‖ut‖4‖ωt‖4‖∇ω‖≤C‖ut‖14‖∇ut‖34‖ωt‖14‖∇ωt‖34‖∇ω‖≤ν+κ4‖∇ut‖2+γ4‖∇ωt‖2+C(‖ut‖2+‖ωt‖2), for t≥t2. | (3.33) |
L3+L4≤ν+κ4‖∇ut‖2+γ2‖∇ωt‖2+C(‖ut‖2+‖ωt‖2). | (3.34) |
By (3.30)–(3.34), we get
ddt(‖ut‖2+‖ωt‖2)≤C(‖ut‖2+‖ωt‖2)+(f1t,ut)+(f2t,ωt)≤C(‖ut‖2+‖ωt‖2)+‖f1t‖2+‖f2t‖2. | (3.35) |
Thanks to
∫t+1t∥f1t(s)∥2ds≤∥f1t∥2L2b≤∥h1∥2L2b,∫t+1t∥f2t(s)∥2ds≤∥f2t∥2L2b≤∥h2∥2L2b, |
and applying uniform Gronwall's inequality to (3.35), we have for any s≥t3+1≡t4,
‖ut(s)‖2+‖ωt(s)‖2≤C. | (3.36) |
Thus, Lemma 3.4 is proved.
Lemma 3.5. Suppose (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). Then, for β>3, there exists a constant ρ6 such that
‖Au(t)‖2+‖Aω(t)‖2≤ρ6, | (3.37) |
for any t≥t4.
Proof. Taking the inner product of −Δu in H1 with the first equation of (1.1), we have
(ν+κ)∥Au∥2+σ∥|u|β−12∇u∥2+4σ(β−1)(β+1)2∥∇|u|β+12∥2=−(ut,Au)−(B(u),Au)+2κ∫Ω∇×ω⋅Audx+(f1(t),Au)≤4(ν+κ)6∥Au∥2+32(ν+κ)∥ut∥2+32(ν+κ)∥B(u)∥2+6κ2ν+κ∥∇ω∥2+32(ν+κ)∥f1(t)∥2. | (3.38) |
Because
32(ν+κ)∥B(u)∥2≤32(ν+κ)∥u∥2∞∥∇u∥2≤3d212(ν+κ)∥∇u∥3∥Δu∥≤ν+κ6∥Au∥2+C∥∇u∥6, | (3.39) |
combining (3.39) with (3.38), we obtain
ν+κ6∥Au∥2≤32(ν+κ)∥ut∥2+C∥∇u∥6+6κ2ν+κ∥∇ω∥2+32(ν+κ)∥f1(t)∥2. | (3.40) |
From the assumption of f01(t), we can easily get
supt∈R∥f1(t)∥≤supt∈R∥f01(t)∥≤K,∀f1∈H(f01). | (3.41) |
By Lemmas 3.2 and 3.4, we obtain
‖Au(t)‖≤C, for any t≥t4. | (3.42) |
Taking the inner product of Aω with (2.1)2, we get
γ‖Aω‖2+4κ∥∇ω∥2+μ∥∇∇⋅ω∥2=−(ωt,Aω)−(B(u,ω),Aω)+2κ(∇×u,Aω)+(f2(t),Aω)≤γ2∥Aω∥2+C(∥ωt∥2+∥B(u,ω)∥2+∥∇u∥2+∥f2(t)∥2). | (3.43) |
And, by Agmon's inequality,
‖B(u,ω)‖2≤C‖u‖2∞‖∇ω‖2≤C‖∇u‖‖Δu‖‖∇ω‖2≤‖Au‖2+C∥∇u∥2∥∇ω∥4. | (3.44) |
From the assumption on f02(t), we can easily obtain
supt∈R∥f2(t)∥≤supt∈R∥f02(t)∥≤K,∀f2∈H(f02). | (3.45) |
By Lemma 3.2, Lemma 3.4, (3.42), (3.43), (3.44), and (3.45), we get
‖Aω(t)‖≤C, for any t≥t4. | (3.46) |
By (3.42) and (3.46), Lemma 3.5 is proved for all t≥t4.
Lemma 3.6. Suppose (uτ,ωτ)∈V1×V2 and (f1,f2)∈H(f01)×H(f02). Then, for β>3, there exists a time t5 and a constant ρ7 satisfying
‖∇ut(t)‖2+‖∇ωt(t)‖2≤ρ7,∀t≥t5. | (3.47) |
Proof. In the proof of Lemma 3.4, from (3.30)–(3.34) we can also get
ddt(∥ut∥2+∥ωt∥2)+ν+κ2∥∇ut∥2+γ2∥∇ωt∥2+2μ∥∇⋅ωt∥2≤C(∥ut∥2+∥ωt∥2)+∥f1(t)∥2+∥f2(t)∥2. | (3.48) |
Integrating (3.48) from t to t+1, and according to Lemma 3.4, we have
∫t+1t(‖∇ut(s)‖2+‖∇ωt(s)‖2+‖∇⋅ωt(s)‖2)ds≤C(‖ut(t)‖2+‖ωt(t)‖2+∫t+1t(‖ut(s)‖2+‖ωt(s)‖2)ds+∫t+1t‖f1t(s)‖2ds+∫t+1t‖f2t(s)‖2ds)≤C+‖h1‖2L2b+‖h2‖2L2b≤C, ∀t≥t4. | (3.49) |
By Lemma 3.5, we get
‖u(t)‖H2+‖ω(t)‖H2≤C,∀t≥t4. | (3.50) |
So, by Lemma 3.2, applying Agmon's inequality, we get
‖u(t)‖∞+‖ω(t)‖∞≤C,∀t≥t4. | (3.51) |
Taking the derivative of (2.1)1 and (2.1)2 with respect to t, then multiplying by Aut and Aωt, respectively, and integrating the resulting equations over Ω, we then have
12ddt(‖∇ut‖2+‖∇ωt‖2)+(ν+κ)‖Aut‖2+γ‖Aωt‖2+4κ‖∇ωt‖2+μ∥∇∇⋅ωt∥2≤|b(ut,u,Aut)|+|b(u,ut,Aut)|+|b(u,ωt,Aωt)|+|b(ut,ω,Aωt)| +2κ∫Ω|∇×ωt⋅Aut|dx+2κ∫Ω|∇×ut⋅Aωt|dx+|∫ΩG′(u)ut⋅Autdx| +(f1t,Aut)+(f2t,Aωt):=9∑i=1Ji. | (3.52) |
For J1, J2, using (2.6) and Lemmas 3.2 and 3.5, we have
J1≤k‖∇ut‖‖∇u‖12‖Au‖12‖Aut‖≤ν+κ5‖Aut‖2+C‖∇ut‖2, ∀t≥t4, | (3.53) |
and
J2≤k‖∇u‖‖∇ut‖12‖Aut‖12‖Aut‖≤k‖∇u‖‖∇ut‖12‖Aut‖32≤ν+κ5‖Aut‖2+C‖∇ut‖2, ∀t≥t4. | (3.54) |
For J3 and J4, similar to (3.53) and (3.54), we get
J3≤k‖∇u‖‖∇ωt‖12‖Aωt‖12‖Aωt‖≤γ4‖Aωt‖2+C‖∇ωt‖2, ∀t≥t4, | (3.55) |
J4≤k‖∇ut‖‖∇ω‖12‖Aω‖12‖Aωt‖≤γ4‖Aωt‖2+C‖∇ut‖2, ∀t≥t4. | (3.56) |
For J5, J6, and J7, applying Hölder's inequality and Young's inequality, we have
J5+J6≤ν+κ5‖Aut‖2+γ4‖Aωt‖2+C(‖∇ut‖2+‖∇ωt‖2), | (3.57) |
and thanks to (3.51),
J7≤C‖u‖β−1∞‖ut‖‖Aut‖≤ν+κ5‖Aut‖2+C‖ut‖2, ∀t≥t4. | (3.58) |
For J8 and J9, we have
J8≤ν+κ5‖Aut‖2+C‖f1t‖2, | (3.59) |
J9≤γ4‖Aωt‖2+C‖f2t‖2. | (3.60) |
By (3.52)–(3.60), we obtain
ddt(‖∇ut‖2+‖∇ωt‖2)≤C(‖∇ut‖2+‖∇ωt‖2)+C‖ut‖2+C(‖f1t‖2+‖f2t‖2). | (3.61) |
Then, by (3.27), (3.49), and using the uniform Gronwall's lemma, we get
‖∇ut(s)‖2+‖∇ωt(s)‖2≤C, ∀s≥t4+1≡t5. | (3.62) |
Thus, Lemma 3.6 is proved.
In this section, we consider the existence of the (V1×V2,V1×V2)-uniform (w.r.t. (f1,f2)∈H(f01)×H(f02)) attractor and the (V1×V2,H2(Ω)×H2(Ω))-uniform attractor for {U(f1,f2)(t,τ)}t≥τ,f1×f2∈H(f01)×H(f02).
Lemma 4.1. Suppose β>3. The family of processes {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02), corresponding to (2.1) is ((V1×V2)×(H(f01)×H(f02)),V1×V2)-continuous for τ≥t5.
Proof. Let τn⊂[τ,+∞) be a time sequence, U(f(n)1,f(n)2)(t,τ)(uτn,ωτn)=(u(n)(t),ω(n)(t)), U(f1,f2)(t,τ)(uτ,ωτ)=(u(t),ω(t)) and
(ˉu(n)(t),ˉω(n)(t))=(u(t)−u(n)(t),ω(t)−ω(n)(t))=U(f1,f2)(t,τ)(uτ,ωτ)−U(f(n)1,f(n)2)(t,τ)(uτn,ωτn). |
It is evident that ˉu(n)(t) is the solution of
∂ˉu(n)(t)∂t+B(u)−B(u(n)(t))+(ν+κ)Aˉu(n)+G(u)−G(u(n))=2κ∇×ˉω(n)+(f1−f(n)1), | (4.1) |
and ˉω(n)(t) is the solution of the following system
∂ˉω(n)(t)∂t+B(u,ω)−B(u(n),ω(n))+4κˉω(n)+γAˉω(n)−μ∇∇⋅ˉω(n)=2κ∇×ˉu(n)+(f2−f(n)2), | (4.2) |
for each n.
Taking the inner product of (4.1) with Aˉu(n) in H1, we get
12ddt‖∇ˉu(n)‖2+b(u,u,Aˉu(n))−b(u(n),u(n),Aˉu(n))+(ν+κ)∥Aˉu(n)∥2+(G(u)−G(u(n)),Aˉu(n))=2κ(∇×ˉω(n),Aˉu(n))+(f1−f(n)1,Aˉu(n)). | (4.3) |
Taking the inner product of (4.2) with Aˉω(n) in H2, we have
12ddt‖∇ˉω(n)‖2+b(u,ω,Aˉω(n))−b(u(n),ω(n),Aˉω(n))+4κ‖∇ˉω(n)‖2+γ∥Aˉω(n)∥2+μ∥∇∇⋅ˉω(n)∥2=2κ(∇×ˉu(n),Aˉω(n))+(f2−f(n)2,Aˉω(n)). | (4.4) |
Combining (4.3) with (4.4), we get
12ddt(‖∇ˉu(n)‖2+‖∇ˉω(n)‖2)+b(u,u,Aˉu(n))−b(u(n),u(n),Aˉu(n))+(ν+κ)‖Aˉu(n)‖2+(G(u)−G(u(n)),Aˉu(n))+b(u,ω,Aˉω(n))−b(u(n),ω(n),Aˉω(n))+4κ∥∇ˉω(n)∥2+γ∥Aˉω(n)∥2+μ∥∇∇⋅ˉω(n)∥2=2κ(∇×ˉω(n),Aˉu(n))+2κ(∇×ˉu(n),Aˉω(n))+(f1−f(n)1,Aˉu(n))+(f2−f(n)2,Aˉω(n)). | (4.5) |
Due to
b(u,u,Aˉu(n))−b(u(n),u(n),Aˉu(n))=b(ˉu(n),u,Aˉu(n))+b(u(n),ˉu(n),Aˉu(n)), | (4.6) |
b(u,ω,Aˉω(n))−b(u(n),ω(n),Aˉω(n))=b(ˉu(n),ω,Aˉω(n))+b(u(n),ˉω(n),Aˉω(n)), | (4.7) |
and
|b(ˉu(n),u,Aˉu(n))|≤k‖∇ˉu(n)‖‖∇u‖12‖Au‖12‖Aˉu(n)‖≤ν+k5‖Aˉu(n)‖2+C‖∇ˉu(n)‖2‖∇u‖‖Au‖, | (4.8) |
|b(u(n),ˉu(n),Aˉu(n))|≤k‖∇u(n)‖‖∇ˉu(n)‖12‖Aˉu(n)‖12‖Aˉu(n)‖≤ν+k5‖Aˉu(n)‖2+C‖∇u(n)‖4‖∇ˉu(n)‖2, | (4.9) |
b(ˉu(n),ω,Aˉω(n))≤k‖∇ˉu(n)‖‖∇ω‖12‖Aω∥12‖Aˉω(n)‖≤γ4‖Aˉω(n)‖2+C‖∇ˉu(n)‖2‖∇ω‖‖Aω‖, | (4.10) |
b(u(n),ˉω(n),Aˉω(n))≤k‖∇u(n)‖‖∇ˉω(n)‖12‖Aˉω(n)‖12‖Aˉω(n)‖≤γ4‖Aˉω(n)‖2+C∥∇u(n)∥4∥∇ˉω(n)∥2, | (4.11) |
2κ|(∇×ˉω(n),Aˉu(n))|≤2κ‖Aˉu(n)‖‖∇ˉω(n)‖≤ν+k5‖Aˉu(n)‖2+C‖∇ˉω(n)‖2, | (4.12) |
2κ|(∇×ˉu(n),Aˉω(n))‖≤2κ∥Aˉω(n)‖‖∇ˉu(n)‖≤γ4‖Aˉω(n)‖2+C‖∇ˉu(n)‖2, | (4.13) |
|(f1−f(n)1,Aˉu(n))|≤ν+k5‖Aˉu(n)‖2+54(ν+κ)‖f1−f(n)1‖2, | (4.14) |
|(f2−f(n)2,Aˉω(n))|≤γ4‖Aˉω(n)‖2+1γ‖f2−f(n)2‖2, | (4.15) |
‖G(u)−G(u(n))‖2=∫Ω|σ|u|β−1u−σ|u(n)|β−1u(n)|2dx≤C∫Ω[|u|β−1|ˉu(n)|+||u|β−1−|u(n)|β−1|⋅|u(n)|]2dx≤C∫Ω|u|2(β−1)|ˉu(n)|2dx+C∫Ω[|u|β−2+|u(n)|β−2]2|u(n)|2|ˉu(n)|2dx≤C[∥u∥2(β−1)∞+(∥u∥2(β−2)∞+∥u(n)∥2(β−2)∞)∥u(n)∥2∞]∥∇ˉu(n)∥2, | (4.16) |
where ˉu(n)(t)=u(t)−un(t). In the above inequality, we used the fact that
|xp−yp|≤cp(|x|p−1+|y|p−1)|x−y| |
for any x,y≥0, where c is an absolute constant.
Therefore,
(G(u)−G(u(n)),Aˉu(n))≤ν+κ5‖Aˉu(n)‖2+54(ν+κ)‖G(u)−G(u(n))‖2≤C[∥u∥2(β−1)∞+(∥u∥2(β−2)∞+∥u(n)∥2(β−2)∞)∥u(n)∥2∞]∥∇ˉu(n)∥2+ν+k5∥Aˉu(n)∥2. | (4.17) |
By (4.5)–(4.15) and (4.17), we obtain
ddt(‖∇ˉu(n)‖2+‖∇ˉω(n)‖2)≤C[∥u∥2(β−1)∞+(∥u∥2(β−2)∞+∥u(n)∥2(β−2)∞)∥u(n)∥2∞+‖∇u‖‖Au‖+‖∇u(n)‖4+‖∇ω‖‖Aω‖+1]⋅(‖∇ˉu(n)‖2+‖∇ˉω(n)‖2)+52(ν+κ)‖f1−f(n)1‖2+2γ‖f2−f(n)2‖2. | (4.18) |
Using Gronwall's inequality in (4.18) yields
‖∇ˉu(n)‖2+‖∇ˉω(n)‖2≤(‖∇ˉu(n)τ‖2+‖∇ˉω(n)τ‖2+52(ν+κ)∫tτ‖f1−f(n)1‖2ds +2γ∫tτ‖f2−f(n)2‖2ds) ⋅exp{C∫tτ[∥u∥2(β−1)∞+(∥u∥2(β−2)∞+∥u(n)∥2(β−2)∞)∥u(n)∥2∞ +‖∇u‖‖Au‖+‖∇u(n)‖4+‖∇ω‖‖Aω‖+1]ds}. | (4.19) |
From Lemmas 3.2 and 3.5, and using Agmon's inequality, we know that
∥u∥∞<C,∥u(n)∥∞<C,∀t≥t5. |
So, from Lemmas 3.2–3.5, we have
exp{C∫tτ[∥u∥2(β−1)∞+(∥u∥2(β−2)∞+∥u(n)∥2(β−2)∞)∥u(n)∥2∞+‖∇u‖‖Au‖+‖∇u(n)‖4+‖∇ω‖‖Aω‖+1]ds}<+∞, |
for any given t and τ, t≥τ, τ≥t5.
Thus, from (4.19), we have that {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) is ((V1×V2)×(H(f01)×H(f02)),V1×V2)-continuous, for τ≥t5.
By Lemma 3.5, the fact of compact imbedding H2×H2↪V1×V2, and Theorem 3.1 in [16], we have the following theorems.
Theorem 4.1. Suppose β>3. The family of processes {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) with respect to problem (1.1) has a (V1×V2,V1×V2) uniform attractor A1. Moreover,
A1=⋃(f1,f2)∈H(f01)×H(f02)K(f1,f2)(0), | (4.20) |
where K(f1,f2)(0) is the section at t=0 of kernel K(f1,f2) of the processes {U(f1,f2)(t,τ)}t≥τ.
Theorem 4.2. Suppose β>3. The family of processes {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) with respect to problem (1.1) has a (V1×V2,H2(Ω)×H2(Ω))-uniform attractor A2. A2 is compact in H2(Ω)×H2(Ω), and it attracts every bounded subset of V1×V2 in the topology of H2(Ω)×H2(Ω).
Proof. By Theorem 2.2, we only need to prove that {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) acting on V1×V2 is (V1×V2,H2(Ω)×H2(Ω))-uniform (w.r.t. f1×f2∈H(f01)×H(f02)) asymptotically compact.
Thanks to Lemma 3.5, we know that B={(u×ω)∈H2×H2:‖Au‖2+‖Aω‖2≤C} is a bounded (V1×V2,H2(Ω)×H2(Ω))-uniform absorbing set of {U(f1,f2)(t,τ)}t≥τ. Then, we just need to prove that, for any τn∈R, any t→+∞, and (uτn,ωτn)∈B, {(un(t),ωn(t))}∞n=0 is precompact in H2(Ω)×H2(Ω), where(un(t),ωn(t))=U(f1,f2)(t,τn)(uτn,ωτn).
Because V1↪H1,V2↪H2 are compact, from Lemma 3.6 we obtain that {ddtun(t)}∞n=0, {ddtωn(t)}∞n=0 are precompact in H1 and H2, respectively.
Next, we will prove {un(t)}∞n=0, {ωn(t)}∞n=0 are Cauchy sequences in H2(Ω). From (2.1), we have
(ν+κ)(Aunk(t)−Aunj(t))=−ddtunk(t)+ddtunj(t)−B(unk(t))+B(unj(t))−G(unk(t))+G(unj(t))+2κ∇×ωnk(t)−2κ∇×ωnj(t). | (4.21) |
γ(Aωnk(t)−Aωnj(t))−μ∇∇⋅ωnk(t)+μ∇∇⋅ωnj(t)=−ddtωnk(t)+ddtωnj(t)−B(unk(t),ωnk(t))+B(unj(t),ωnj(t))−4κωnk(t)+4κωnj(t)+2κ∇×unk(t)−2κ∇×unj(t). | (4.22) |
Multiplying (4.21) by Aunk(t)−Aunj(t), we obtain
(ν+κ)∥Aunk(t)−Aunj(t)∥2≤∥ddtunk(t)−ddtunj(t)∥⋅∥Aunk(t)−Aunj(t)∥+∥B(unk(t))−B(unj(t))∥⋅∥Aunk(t)−Aunj(t)∥+∥G(unk(t))−G(unj(t))∥⋅∥Aunk(t)−Aunj(t)∥ +2κ∥∇ωnk(t)−∇ωnj(t)∥⋅∥Aunk(t)−Aunj(t)∥≤4(ν+κ)5∥Aunk(t)−Aunj(t)∥2+54(ν+κ)∥ddtunk(t)−ddtunj(t)∥2 +54(ν+κ)∥B(unk(t))−B(unj(t))∥2+54(ν+κ)∥G(unk(t))−G(unj(t))∥2 +5κ2ν+κ∥∇ωnk(t)−∇ωnj(t)∥2, |
so we have
ν+κ5∥Aunk(t)−Aunj(t)∥2≤54(ν+κ)∥ddtunk(t)−ddtunj(t)∥2 +54(ν+κ)∥B(unk(t))−B(unj(t))∥2 +54(ν+κ)∥G(unk(t))−G(unj(t))∥2 +5κ2ν+κ∥∇ωnk(t)−∇ωnj(t)∥2. | (4.23) |
Multiplying (4.22) by Aωnk(t)−Aωnj(t) we obtain
γ∥Aωnk(t)−Aωnj(t)∥2+μ∥∇∇⋅(ωnk(t)−ωnj(t))∥2≤∥ddtωnk(t)−ddtωnj(t)∥⋅∥Aωnk(t)−Aωnj(t)∥+∥B(unk(t),ωnk(t))−B(unj(t),ωnj(t))∥ ⋅∥Aωnk(t)−Aωnj(t)∥+4κ∥ωnk(t)−ωnj(t)∥⋅∥Aωnk(t)−Aωnj(t)∥ +2κ∥∇unk(t)−∇unj(t)∥⋅∥Aωnk(t)−Aωnj(t)∥≤4γ5∥Aωnk(t)−Aωnj(t)∥2+54γ∥ddtωnk(t)−ddtωnj(t)∥2 +54γ∥B(unk(t),ωnk(t))−B(unj(t),ωnj(t))∥2+20κ2γ∥ωnk(t)−ωnj(t))∥2 +5κ2γ∥∇unk(t)−∇unj(t)∥2, |
so we get
γ5∥Aωnk(t)−Aωnj(t)∥2+μ∥∇∇⋅(ωnk(t)−ωnj(t))∥2≤54γ∥ddtωnk(t)−ddtωnj(t)∥2+54γ∥B(unk(t),ωnk(t))−B(unj(t),ωnj(t))∥2 +20κ2γ∥ωnk(t)−ωnj(t)∥2+5κ2γ∥∇unk(t)−∇unj(t)∥2. | (4.24) |
Combining (4.23) with (4.24), we have
ν+κ5∥Aunk(t)−Aunj(t)∥2+γ5∥Aωnk(t)−Aωnj(t)∥2≤54(ν+κ)∥ddtunk(t)−ddtunj(t)∥2+54(ν+κ)∥B(unk(t))−B(unj(t))∥2 +54(ν+κ)∥G(unk(t))−G(unj(t))∥2+5κ2ν+κ∥∇ωnk(t)−∇ωnj(t)∥2 +54γ∥ddtωnk(t)−ddtωnj(t)∥2+54γ∥B(unk(t),ωnk(t))−B(unj(t),ωnj(t))∥2 +20κ2γ∥ωnk(t)−ωnj(t)∥2+5κ2γ∥∇unk(t)−∇unj(t)∥2. | (4.25) |
Because V2↪H2 is compact, from Lemma 3.2 we know that {ωn(t)}∞n=0 is precompact in H2. And, using the compactness of embedding H2(Ω)↪V1,H2(Ω)↪V2 and Lemma 3.5, we have that {un(t)}∞n=0,{ωn(t)}∞n=0 are precompact in V1 and V2, respectively. Considering V1↪H1,V2↪H2 are compact, from Lemma 3.6 we know that {ddtun(t)}∞n=0, {ddtωn(t)}∞n=0 are precompact in H1 and H2, respectively.
Using (2.6), we have
∥B(unk(t))−B(unj(t))∥2≤C(∥B(unk(t),unk(t)−unj(t))∥2+∥B(unk(t)−unj(t),unj(t))∥2)≤C(∥∇unk(t)∥2∥∇(unk(t)−unj(t))∥∥A(unk(t)−unj(t))∥ +∥∇(unk(t)−unj(t))∥2∥∇unj(t)∥∥Aunj(t)∥)→0,as k,j→+∞, | (4.26) |
and
∥B(unk(t),ωnk(t))−B(unj(t),ωnj(t))∥2≤C(∥B(unk(t),ωnk(t)−ωnj(t))∥2+∥B(unk(t)−unj(t),ωnj(t))∥2)≤C(∥∇unk(t)∥2∥∇(ωnk(t)−ωnj(t))∥∥A(ωnk(t)−ωnj(t))∥ +∥∇(unk(t)−unj(t))∥2∥∇ωnj(t)∥∥Aωnj(t)∥)→0, as k,j→+∞. | (4.27) |
From the proof of Lemma 4.2 in [15], we have
∥G(unk(t))−G(unj(t))∥2≤C∥unk(t)−unj(t)∥2→0, as k,j→+∞. | (4.28) |
Taking into account (4.25)–(4.28), we have
ν+κ5∥Aunk(t)−Aunj(t)∥2+γ5∥Aωnk(t)−Aωnj(t)∥2→0, as k,j→+∞. | (4.29) |
(4.29) indicates that the processes {U(f1,f2)(t,τ)}t≥τ are uniformly asymptotically compact in H2(Ω)×H2(Ω). So, by Theorem 2.2, it has a (V1×V2,H2(Ω)×H2(Ω))-uniform attractor A2.
Theorem 4.3. Suppose β>3. The (V1×V2,V1×V2)-uniform attractor A1 of the family of processes {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) is actually the (V1×V2,H2(Ω)×H2(Ω))-uniform attractor A2, i.e., A1=A2.
Proof. First, we will prove A1⊂A2. Because A2 is bounded in H2(Ω)×H2(Ω), and the embedding H2(Ω)×H2(Ω)↪V1×V2 is continuous, A2 is bounded in V1×V2. From Theorem 4.2, we know that A2 attracts uniformly all bounded subsets of V1×V2, so A2 is a bounded uniform attracting set of {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) in V1×V2. By the minimality of A1, we have A1⊂A2.
Now, we will prove A2⊂A1. First, we will prove A1 is a (V1×V2,H2(Ω)×H2(Ω))-uniformly attracting set of {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02). That is to say, we will prove
limt→+∞(sup(f1,f2)∈H(f01)×H(f02)distH2(Ω)×H2(Ω)(U(f1,f2)(t,τ)B,A1))=0, | (4.30) |
for any τ∈R and B∈B(V1×V2).
If we suppose (4.30) is not valid, then there must exist some τ∈R, B∈B(V1×V2), ε0>0, (f(n)1,f(n)2)∈H(f01)×H(f02), and tn→+∞, when n→+∞, such that, for all n≥1,
distH2(Ω)×H2(Ω)(U(f(n)1,f(n)2)(tn,τ)B,A1)≥2ε0. | (4.31) |
This shows that there exists (un,ωn)∈B such that
distH2(Ω)×H2(Ω)(U(f(n)1,f(n)2)(tn,τ)(un,ωn),A1)≥ε0. | (4.32) |
In the light of Theorem 4.2, {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) has a (V1×V2,H2(Ω)×H2(Ω))-uniform attractor A2 which attracts any bounded subset of V1×V2 in the topology of H2(Ω)×H2(Ω). Therefore, there exists (ζ,η)∈H2(Ω)×H2(Ω) and a subsequence of U(f(n)1,f(n)2)(tn,τ)(un,ωn) such that
U(f(n)1,f(n)2)(tn,τ)(un,ωn)→(ζ,η)strongly in H2(Ω)×H2(Ω). | (4.33) |
On the other side, the processes {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02) have a (V1×V2,V1×V2)-uniform attractor A1, which attracts uniformly any bounded subsets of V1×V2 in the topology of V1×V2. So, there exists (u,ω)∈V1×V2 and a subsequence of U(f(n)1,f(n)2)(tn,τ)(un,ωn) such that
U(f(n)1,f(n)2)(tn,τ)(un,ωn)→(u,ω) strongly in V1×V2. | (4.34) |
From (4.33) and (4.34), we have (u,ω)=(ζ,η), so (4.33) can also be written as
U(f(n)1,f(n)2)(tn,τ)(un,ωn)→(u,ω) strongly in H2(Ω)×H2(Ω). | (4.35) |
And, from Theorem 4.1, we know that A1 attracts B, so
limn→+∞distV1×V2(U(f(n)1,f(n)2)(tn,τ)(un,ωn),A1)=0. | (4.36) |
By (4.34), (4.36), and the compactness of A1 in V1×V2, we have (u,ω)∈A1. Considering (4.35), we have
limn→+∞distH2(Ω)×H2(Ω)(U(f(n)1,f(n)2)(tn,τ)(un,ωn),A1)≤limn→+∞distH2(Ω)×H2(Ω)(U(f(n)1,f(n)2)(tn,τ)(un,ωn),(u,ω))=0, |
which contradicts (4.32). Therefore, A1 is a (V1×V2,H2(Ω)×H2(Ω))-uniform attractor of {U(f1,f2)(t,τ)}t≥τ, f1×f2∈H(f01)×H(f02), and by the minimality of A2, we have A2⊂A1.
In this paper, we discussed the existence of uniform attractors of strong solutions for 3D incompressible micropolar equations with nonlinear damping. Based on some translation-compactness assumption on the external forces, and when β>3, we made a series of uniform estimates on the solutions in various functional spaces. According to these uniform estimates, we proved the existence of uniform attractors for the process operators corresponding to the solution of the equation in V1×V2 and H2×H2, and verified that the uniform attractors in V1×V2 and H2×H2 are actually the same.
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
The authors are thankful to the editors and the anonymous reviewers for their valuable suggestions and comments on the manuscript. This work is supported by National Natural Science Foundation of China (Nos. 11601417, 12001420).
The authors declare no conflict of interest in this paper.
[1] |
Garrod AE (1902) The Incidence of Alkaptonuria: A Study in Chemical Individuality. Lancet 2: 1616-1620. doi: 10.1016/S0140-6736(01)41972-6
![]() |
[2] | Garrod AE (1908) The Croonian Lectures on inborn errors of metabolism, lecture II Alkaptonuria. Lancet 2: 73-79. |
[3] |
Phornphutkul C, Introne WJ, Perry MB, et al. (2002) Natural history of alkaptonuria. N Engl J Med 347: 2111-2121. doi: 10.1056/NEJMoa021736
![]() |
[4] | Mistry JB, Bukhari M, Taylor AM (2013) Alkaptonuria. Rare Dis 1: 1-7. |
[5] |
La Du BN, Zannoni VG, Laster L, et al. (1958) The nature of the defect in tyrosine metabolism in alcaptonuria. J Biol Chem 230: 251-260. doi: 10.1016/S0021-9258(18)70560-7
![]() |
[6] |
Al-Shagahin HM, Mwafi N, Khasawneh M, et al. (2019) Ear, nose, and throat manifestations of alkaptonuria patients from Jordan. Indian J Otol 25: 109-113. doi: 10.4103/indianjotol.INDIANJOTOL_23_19
![]() |
[7] |
Sakthivel S, Zatkova A, Nemethova M, et al. (2014) Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence. Ann Hum Genet 78: 155-164. doi: 10.1111/ahg.12055
![]() |
[8] | Helliwell TR, Gallagher JA, Ranganath L (2008) Alkaptonuria--a review of surgical and autopsy pathology. Histopathology 53: 503-512. |
[9] |
Fernandez-Canon JM, Granadino B, Beltran-Valero de Bernabe D, et al. (1996) The molecular basis of alkaptonuria. Nat Genet 14: 19-24. doi: 10.1038/ng0996-19
![]() |
[10] |
Zatkova A (2011) An update on molecular genetics of Alkaptonuria (AKU). J Inherit Metab Dis 34: 1127-1136. doi: 10.1007/s10545-011-9363-z
![]() |
[11] |
Alsbou M, Mwafi N (2013) A previously undiagnosed case of alkaptonuria: A case report. Turk J Rheumatol 28: 132-135. doi: 10.5606/tjr.2013.2660
![]() |
[12] | Ranganath LR, Milan AM, Hughes AT, et al. (2020) Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre. JIMD Rep 1-13. |
[13] |
Zatkova A, Ranganath L, Kadasi L (2020) Alkaptonuria: Current Perspectives. Appl Clin Genet 13: 37-47. doi: 10.2147/TACG.S186773
![]() |
[14] |
Ranganath LR, Jarvis JC, Gallagher JA (2013) Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol 66: 367-373. doi: 10.1136/jclinpath-2012-200877
![]() |
[15] |
Taylor AM, Boyde A, Wilson PJ, et al. (2011) The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuria. Arthritis Rheum 63: 3887-3896. doi: 10.1002/art.30606
![]() |
[16] | Wu K, Bauer E, Myung G, et al. (2018) Musculoskeletal manifestations of alkaptonuria: A case report and literature review. Eur J Rheumatol 6: 98-101. |
[17] |
Thapa M, Yu J, Lee W, et al. (2015) Determination of homogentisic acid in human plasma by GC-MS for diagnosis of alkaptonuria. Anal Sci Technol 28: 323-330. doi: 10.5806/AST.2015.28.5.323
![]() |
[18] | Groseanu L, Marinescu R, Laptoiun D, et al. (2010) A late and difficult diagnosis of ochronosis. J Med Life 3: 437-443. |
[19] |
Balaban B, Taskaynatan M, Yasar E, et al. (2006) Ochronotic spondyloarthropathy: Spinal involvement resembling ankylosing spondylitis. Clin Rheumatol 25: 598-601. doi: 10.1007/s10067-005-0038-8
![]() |
[20] |
Ranganath LR, Milan AM, Hughes AT, et al. (2016) Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment. Ann Rheum Dis 75: 362-367. doi: 10.1136/annrheumdis-2014-206033
![]() |
[21] |
Ranganath LR, Psarelli EE, Arnoux J, et al. (2020) Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol 8: 762-772. doi: 10.1016/S2213-8587(20)30228-X
![]() |
[22] |
Ranganath LR, Khedr M, Milan AM, et al. (2018) Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre. Mol Genet Metab 125: 127-134. doi: 10.1016/j.ymgme.2018.07.011
![]() |
[23] |
Keenan CM, Preston AJ, Sutherland H, et al. (2015) Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice. JIMD Rep 24: 45-50. doi: 10.1007/8904_2015_437
![]() |
[24] |
Khedr M, Judd S, Briggs MC, et al. (2018) Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria. JIMD Rep 40: 31-37. doi: 10.1007/8904_2017_62
![]() |
[25] |
Hughes JH, Wilson P, Sutherland H, et al. (2020) Dietary restriction of tyrosine and phenylalanine lowers tyrosinemia associated with nitisinone therapy of alkaptonuria. J Inherit Metab Dis 43: 259-268. doi: 10.1002/jimd.12172
![]() |
[26] |
Kılavuz S, Derya Bulut F, Kör D, et al. (2018) Demographic, Phenotypic and Genotypic Features of Alkaptonuria Patients: A Single Centre Experience. J Pediatr Res 3: 7-11. doi: 10.4274/jpr.20982
![]() |
[27] |
Ascher DB, Spiga O, Sekelska M, et al. (2019) Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype–phenotype correlations in the largest cohort of patients with AKU. Eur J Hum Genet 27: 888-902. doi: 10.1038/s41431-019-0354-0
![]() |
[28] |
Zatkova A, Sedlackova T, Radvansky J, et al. (2012) Identification of 11 Novel Homogentisate 1, 2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database. JIMD Rep 4: 55-65. doi: 10.1007/8904_2011_68
![]() |
[29] |
Abdulrazzaq YM, Ibrahim A, Al-khayat AI, et al. (2009) R58fs mutation in the HGD gene in a family with alkaptonuria in the UAE. Ann Hum Genet 73: 125-130. doi: 10.1111/j.1469-1809.2008.00485.x
![]() |
[30] |
Ladjouze-Rezig A, Rodriguez de Cordoba S, Aquaron R (2006) Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies- a case study of 14 patients in 11 families. Joint Bone Spine 73: 284-292. doi: 10.1016/j.jbspin.2005.03.010
![]() |
[31] |
Al-Sbou M, Mwafi N, Lubad MA (2012) Identification of forty cases with alkaptonuria in one village in Jordan. Rheumatol Int 32: 3737-3740. doi: 10.1007/s00296-011-2219-x
![]() |
[32] |
Nemethova M, Radvanszky J, Kadasi L, et al. (2016) Twelve novel HGD gene variants identified in 99 alkaptonuria patients: Focus on “black bone disease” in Italy. Eur J Hum Genet 24: 66-72. doi: 10.1038/ejhg.2015.60
![]() |
[33] |
Koressaar T, Remm M (2007) Enhancements and modifications of primer design program Primer3. Bioinformatics 23: 1289-1291. doi: 10.1093/bioinformatics/btm091
![]() |
[34] |
Untergasser A, Cutcutache I, Koressaar T, et al. (2012) Primer3-new capabilities and interfaces. Nucleic Acids Res 40: e115. doi: 10.1093/nar/gks596
![]() |
[35] | Zatkova A, Nemethova M (2015) Genetics of alkaptonuria – an overview. Eur Pharm J 62: 27-32. |
[36] |
Ben Halim N, Ben Alaya Bouafif N, Romdhane L, et al. (2013) Consanguinity, endogamy, and genetic disorders in Tunisia. J Community Genet 4: 273-284. doi: 10.1007/s12687-012-0128-7
![]() |
[37] | Hamamy HA, Masri AT, Al-Hadidy AM, et al. (2007) Consanguinity and genetic disorders. Profile from Jordan. Saudi Med J 28: 1015-1017. |
[38] |
Titus GP, Mueller HA, Burgner J, et al. (2000) Crystal structure of human homogentisate dioxygenase. Nat Struct Biol 7: 542-546. doi: 10.1038/76756
![]() |
[39] |
Usher J, Ascher D, Pires D, et al. (2015) Analysis of HGD Gene Mutations in Patients with Alkaptonuria from the United Kingdom: Identification of Novel Mutations. JIMD Rep 24: 3-11. doi: 10.1007/8904_2014_380
![]() |
[40] |
Bernini A, Galderisi S, Spiga O, et al. (2017) Toward a generalized computational workflow for exploiting transient pockets as new targets for small molecule stabilizers: application to the homogentisate 1,2-dioxygenase mutants at the base of rare disease Alkaptonuria. Comput Biol Chem 70: 133-141. doi: 10.1016/j.compbiolchem.2017.08.008
![]() |
[41] |
Vilboux T, Kayser M, Introne W, et al. (2009) Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria. Hum Mutat 30: 1611-1619. doi: 10.1002/humu.21120
![]() |
[42] |
Beltrán-Valero De Bernabé D, Granadino B, Chiarelli I, et al. (1998) Mutation and polymorphism analysis of the human homogentisate 1,2-dioxygenase gene in alkaptonuria patients. Am J Hum Genet 62: 776-784. doi: 10.1086/301805
![]() |