Dynamics and implications of models for intermittent androgen suppression therapy

Tin Phan; Changhan He; Alejandro Martinez; Yang Kuang; Tin Phan; Changhan He; Alejandro Martinez; Yang Kuang

doi:10.3934/mbe.2019010

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 1: 187-204. doi: 10.3934/mbe.2019010

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Research article Special Issues

Dynamics and implications of models for intermittent androgen suppression therapy

1.
School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ 85287, USA
2.
Department of Physics,Department of Physics, Tempe, AZ 85287, USA

Received: 11 October 2018 Accepted: 12 October 2018 Published: 11 December 2018

In this paper, we formulate a three cell population model of intermittent androgen suppression therapy for cancer patients to study the treatment resistance development. We compare it with other models that have different underlying cell population structure using patient prostate specific antigen (PSA) and androgen data sets. Our results show that in the absence of extensive data, a two cell population structure performs slightly better in replicating and forecasting the dynamics observed in clinical PSA data. We also observe that at least one absorbing state should be present in the cell population structure of a plausible model for it to produce treatment resistance under continuous hormonal therapy. This suggests that the heterogeneity of prostate cancer cell population can be represented by two types of cells differentiated by their level of dependence on androgen, where the two types are linked via an irreversible transformation.

Keywords:

Citation: Tin Phan, Changhan He, Alejandro Martinez, Yang Kuang. Dynamics and implications of models for intermittent androgen suppression therapy[J]. Mathematical Biosciences and Engineering, 2019, 16(1): 187-204. doi: 10.3934/mbe.2019010

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Abstract

1. Introduction

In 1960, Opial ^[12] established the following inequality:

Theorem A Suppose $f\in C^{1}[0, h]$ satisfies $f(0) = f(h) = 0$ and $f(x) > 0$ for all $x\in (0, h).$ Then the inequality holds

$\begin{align} \int_{0}^h\left|f(x)f'(x)\right|dx\leq\frac{h}{4}\int_{0}^{h}(f'(x))^{2}dx, \end{align}$

(1.1)

where this constant $h/4$ is best possible.

Many generalizations and extensions of Opial's inequality were established ^{[2,4,5,6,7,8,9,10,11,15,16,17,18,19]}. For an extensive survey on these inequalities, see ^[13]. Opial's inequality and its generalizations and extensions play a fundamental role in the ordinary and partial differential equations as well as difference equation ^{[2,3,4,6,7,9,10,11,17]}. In particular, Agarwal and Pang ^[3] proved the following Opial-Wirtinger's type inequalities.

Theorem B Let $\lambda\geq 1$ be a given real number, and let $p(t)$ be a nonnegative and continuous function on $[0, a]$ . Further, let $x(t)$ be an absolutely continuous function on $[0, a]$ , with $x(0) = x(a) = 0$ . Then

$\begin{align} \int_{0}^{a}p(t)|x(t)|^{\lambda}dt\leq\frac{1}{2}\int_{0}^{a}[t(a-t)]^{(\lambda-1)/2}p(t)dt\int_{0}^{a}\left|x'(t) \right|^{\lambda}dt. \end{align}$

(1.2)

The first aim of the present paper is to establish Opial-Wirtinger's type inequalities involving Katugampola conformable partial derivatives and $\alpha$ -conformable integrals (see Section 2). Our result is given in the following theorem, which is a generalization of (1.2).

Theorem 1.1 Let $\lambda\geq 1$ be a real number and $\alpha\in (0, 1]$ , and let $p(s, t)$ be a nonnegative and continuous functions on $[0, a]\times [0, b]$ . Further, let $x(s, t)$ be an absolutely continuous function and Katugampola partial derivable on $[0, a]\times [0, b]$ , with $x(s, 0) = x(0, t) = x(0, 0) = 0$ and $x(a, b) = x(a, t) = x(s, b) = 0$ . If $p > 1,$ $\frac{1}{p}+\frac{1}{q} = 1$ Then

$\int_{0}^{a}\int_{0}^{b}p(s, t)|x(s, t)|^{\lambda}d_{\alpha}sd_{\alpha}t\leq\frac{p+q}{pq} \left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\left(\int_{0}^{a}\int_{0}^{b}\Gamma_{abpq\lambda\alpha}(s, t)\cdot p(s, t)d_{\alpha}sd_{\alpha}t\right)$

$\begin{align} \times\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t, \end{align}$

(1.3)

where

$\Gamma_{abpq\lambda\alpha}(s, t) = \left\{(st)^{1/p}[(a-s)(b-t)]^{1/q}\right\}^{\alpha(\lambda-1)}.$

Remark 1.1 Let $x(s, t)$ reduce to $s(t)$ and with suitable modifications, and $p = q = 2$ and $\alpha = 1$ , (1.3) become (1.2).

Theorem C Let $\lambda\geq 1$ be a given real number, and let $p(t)$ be a nonnegative and continuous function on $[0, a]$ . Further, let $x(t)$ be an absolutely continuous function on $[0, a]$ , with $x(0) = x(a) = 0$ . Then

$\begin{align} \int_{0}^{a}p(t)|x(t)|^{\lambda}dt\leq\frac{1}{2}\left(\frac{a}{2} \right)^{\lambda-1}\left(\int_{0}^{a}p(t)dt\right)\int_{0}^{a}\left|x'(t)\right|^{\lambda}dt. \end{align}$

(1.4)

Another aim of this paper is to establish the following inequality involving Katugampola conformable partial derivatives and $\alpha$ -conformable integrals. Our result is given in the following theorem.

Theorem 1.2 Let $j = 1, 2$ and $\lambda\geq 1$ be a real number, and let $p_{j}(s, t)$ be a nonnegative and continuous functions on $[0, a]\times [0, b]$ . Further, let $x_{j}(s, t)$ be an absolutely continuous function and Katugampola partial derivable on $[0, a]\times [0, b]$ , with $x_{j}(s, 0) = x_{j}(0, t) = x_{j}(0, 0) = 0$ and $x_{j}(a, b) = x_{j}(a, t) = x_{j}(s, b) = 0$ . Then for $\alpha\in(0, 1]$

$\int_{0}^{a}\int_{0}^{b}\left(p_{1}(s, t)|x_{1}(s, t)|^{\lambda}+p_{2}(s, t)|x_{2}(s, t)|^{\lambda}\right)d_{\alpha}sd_{\alpha}t\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\leq\frac{1}{2^{\lambda}}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\Bigg[\left(\int_{0}^{a}\int_{0}^{b}(st)^{\alpha(\lambda-1)}p_{1}(s, t) d_{\alpha}sd_{\alpha}t\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)\right|^{\lambda} d_{\alpha}sd_{\alpha}t$

$\begin{align} +\left(\int_{0}^{a}\int_{0}^{b}(st)^{\alpha(\lambda-1)}p_{2}(s, t)d_{\alpha}sd_{\alpha}t\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{2})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\Bigg]. \end{align}$

(1.5)

2. Katugampola conformable partial derivatives

Here, let's recall the well-known Katugampola derivative formulation of conformable derivative of order for $\alpha\in(0, 1]$ and $t\in[0, \infty)$ , given by

$\begin{align} {\cal D}_{\alpha}(f)(t) = \lim\limits_{\varepsilon\rightarrow 0}\frac{f(te^{\varepsilon t^{-\alpha}})-f(t)}{\varepsilon}, \end{align}$

(2.1)

and

$\begin{align} {\cal D}_{\alpha}(f)(0) = \lim\limits_{t\rightarrow 0}D_{\alpha}(f)(t), \end{align}$

(2.2)

provided the limits exist. If $f$ is fully differentiable at $t$ , then

${\cal D}_{\alpha}(f)(t) = t^{1-\alpha}\frac{df}{dt}(t).$

A function $f$ is $\alpha$ -differentiable at a point $t\geq 0$ , if the limits in (2.1) and (2.2) exist and are finite. Inspired by this, we propose a new concept of $\alpha$ -conformable partial derivative. In the way of (1.4), $\alpha$ -conformable partial derivative is defined in as follows:

Definition 2.1 ^[20] ( $\alpha$ -conformable partial derivative) Let $\alpha\in (0, 1]$ and $s, t\in[0, \infty)$ . Suppose $f(s, t)$ is a continuous function and partial derivable, the $\alpha$ -conformable partial derivative at a point $s\geq 0$ , denoted by $\frac{\partial}{\partial s}(f)_{\alpha}(s, t)$ , defined by

$\begin{align} \frac{\partial}{\partial s}(f)_{\alpha}(s, t) = \lim\limits_{\varepsilon\rightarrow 0}\frac{f(se^{\varepsilon s^{-\alpha}}, t)-f(s, t)} {\varepsilon}, \end{align}$

(2.3)

provided the limits exist, and call $\alpha$ -conformable partial derivable.

Recently, Katugampola conformable partial derivative is defined in as follows:

Definition 2.2 ^[20] (Katugampola conformable partial derivatives) Let $\alpha\in (0, 1]$ and $s, t\in[0, \infty)$ . Suppose $f(s, t)$ and $\frac{\partial}{\partial s}(f)_{\alpha}(s, t)$ are continuous functions and partial derivable, the Katugampola conformable partial derivative, denoted by $\frac{\partial^{2}}{\partial s\partial t}(f)_{\alpha^{2}}(s, t)$ , defined by

$\begin{align} \frac{\partial^{2}}{\partial s\partial t}(f)_{\alpha^{2}}(s, t) = \lim\limits_{\varepsilon\rightarrow 0}\frac{\frac{\partial}{\partial s}(f)_{\alpha}(s, te^{\varepsilon t^{-\alpha}})-\frac{\partial}{\partial s}(f)_{\alpha}(s, t)}{\varepsilon}, \end{align}$

(2.4)

provided the limits exist, and call Katugampola conformable partial derivable.

Definition 2.3 ^[20] ( $\alpha$ -conformable integral) Let $\alpha\in (0, 1]$ , $0\leq a < b$ and $0\leq c < d$ . A function $f(x, y):[a, b]\times[c, d]\rightarrow {\Bbb R}$ is $\alpha$ -conformable integrable, if the integral

$\begin{align} \int_{a}^{b}\int_{c}^{d}f(x, y)d_{\alpha}xd_{\alpha}y: = \int_{a}^{b}\int_{c}^{d} (xy)^{\alpha-1}f(x, y)dxdy \end{align}$

(2.5)

exists and is finite.

3. Main results

Theorem 3.1 Let $\lambda\geq 1$ be a real number and $\alpha\in (0, 1]$ , and let $p(s, t)$ be a nonnegative and continuous functions on $[0, a]\times [0, b]$ . Further, let $x(s, t)$ be an absolutely continuous function and Katugampola partial derivable on $[0, a]\times [0, b]$ , with $x(s, 0) = x(0, t) = x(0, 0) = 0$ and $x(a, b) = x(a, t) = x(s, b) = 0$ . If $p > 1,$ $\frac{1}{p}+\frac{1}{q} = 1$ Then

$\begin{align} \times\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t, \end{align}$

(3.1)

where

$\Gamma_{abpq\lambda\alpha}(s, t) = \left\{(st)^{1/p}[(a-s)(b-t)]^{1/q}\right\}^{\alpha(\lambda-1)}.$

Proof From (2.4) and (2.5), we have

$x(s, t) = \int_{0}^{s}\int_{0}^{t}\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)d_{\alpha}sd_{\alpha}t.$

By using Hölder's inequality with indices $\lambda$ and $\lambda/(\lambda-1)$ , we have

$|x(s, t)|^{\lambda/p}\leq \left[\left(\int_{0}^{s}\int_{0}^{t}\left|\frac{\partial^{2}}{\partial s\partial t} (x)_{\alpha^{2}}(s, t)\right|d_{\alpha}sd_{\alpha}t\right)^{\lambda}\right]^{1/p}\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\begin{align} \leq\left(\frac{1}{\alpha^{2}}(st)^{\alpha}\right)^{(\lambda-1)/p}\left(\int_{0}^{s}\int_{0}^{t}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)^{1/p}. \end{align}$

(3.2)

Similarly, from

$x(s, t) = \int_{s}^{a}\int_{t}^{b}\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)d_{\alpha}sd_{\alpha}t,$

we obtain

$\begin{align} |x(s, t)|^{\lambda/q}\leq \left(\frac{1}{\alpha^{2}}[(a-s)(b-t)]^{\alpha}\right)^{(\lambda-1)/q} \left(\int_{s}^{a}\int_{t}^{b}\left|\frac{\partial^{q}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)^{1/q}. \end{align}$

(3.3)

Now a multiplication of (3.2) and (3.3), and by using the well-known Young inequality gives

$\begin{eqnarray*} |x(s, t)|^{\lambda}&\leq &\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\Gamma_{abpq\lambda\alpha}(s, t)\cdot\left(\int_{0}^{s}\int_{0}^{t} \left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)^{1/p}\\ &\times&\left(\int_{s}^{a}\int_{t}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)^{1/q}\\ &\leq &\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\Gamma_{abpq\lambda\alpha}(s, t)\cdot\Bigg(\frac{1}{p}\int_{0}^{s}\int_{0}^{t}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\\ &+&\frac{1}{q}\int_{s}^{a}\int_{t}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\Bigg) \end{eqnarray*}$

$\begin{align} \; \; \; \; \; \; \; \; \; \; = \frac{p+q}{pq}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\Gamma_{abpq\lambda\alpha}(s, t)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t, \end{align}$

(3.4)

where

$\Gamma_{abpq\lambda\alpha}(s, t) = \Big\{(st)^{1/p}[(a-s)(b-t)]^{1/q}\Big\} ^{\alpha(\lambda-1)}.$

Multiplying the both sides of (3.4) by $p(s, t)$ and $\alpha$ –conformable integrating both sides over $t$ from $0$ to $b$ first and then integrating the resulting inequality over $s$ from $0$ to $a$ , we obtain

$\int_{0}^{a}\int_{0}^{b}p(s, t)|x(s, t)|^{\lambda}d_{\alpha}sd_{\alpha}t\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\leq\frac{p+q}{pq}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\int_{0}^{a}\int_{0}^{b}\Gamma_{abpq\lambda\alpha}(s, t)\cdot p(s, t)\left(\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)d_{\alpha}sd_{\alpha}t$

$= \frac{p+q}{pq}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\left(\int_{0}^{a}\int_{0}^{b}\Gamma_{abpq\lambda\alpha}(s, t)\cdot p(s, t)d_{\alpha}sd_{\alpha}t\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t.$

This completes the proof.

Remark 3.1 Let $x(s, t)$ reduce to $s(t)$ and with suitable modifications, (3.1) becomes the following result.

$\begin{align} \int_{0}^{a}p(t)|x(t)|^{\lambda}d_{\alpha}t\leq\frac{p+q}{pq}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\cdot\int_{0}^{a} \Gamma_{apq\lambda\alpha}(t)p(t)d_{\alpha}t\int_{0}^{a}\left|{\cal D}_{\alpha}(x)(t) \right|^{\lambda}d_{\alpha}t, \end{align}$

(3.5)

where ${\cal D}_{\alpha}(x)(t)$ is Katugampola derivative (2.1) stated in the introduction, and

$\Gamma_{apq\lambda\alpha}(t) = \Big\{t^{1/p}(a-t)^{1/q}\Big\} ^{\alpha(\lambda-1)}.$

Putting $p = q = 2$ and $\alpha = 1$ in (3.5), (3.5) becomes inequality (1.2) established by Agarwal and Pang ^[3] stated in the introduction.

Taking for $\alpha = 1$ , $p = q = 2$ and $p(s, t) = {\rm constant}$ in (3.1), we have the following interesting result.

$\int_{0}^{a}\int_{0}^{b}|x(s, t)|^{\lambda}dsdt\leq \frac{1}{2}(ab)^{\lambda}\left[B\left(\frac{\lambda+1}{2}, \frac{\lambda+1}{2}\right)\right] ^{2}\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}x(s, t)\right|^{\lambda}dsdt,$

where $B$ is the Beta function.

Theorem 3.2 Let $j = 1, 2$ and $\lambda\geq 1$ be a real number, and let $p_{j}(s, t)$ be a nonnegative and continuous functions on $[0, a]\times [0, b]$ . Further, let $x_{j}(s, t)$ be an absolutely continuous function and Katugampola partial derivable on $[0, a]\times [0, b]$ , with $x_{j}(s, 0) = x_{j}(0, t) = x_{j}(0, 0) = 0$ and $x_{j}(a, b) = x_{j}(a, t) = x_{j}(s, b) = 0$ . Then for $\alpha\in(0, 1]$

(3.6)

Proof Because

$x_{1}(s, t) = \int_{0}^{s}\int_{0}^{t}\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)d_{\alpha}sd_{\alpha}t = \int_{s}^{a}\int_{t}^{b}\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)d_{\alpha}sd_{\alpha}t.$

Hence

$|x_{1}(s, t)|\leq\frac{1}{2}\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)\right|d_{\alpha}sd_{\alpha}t.$

By Hölder's inequality with indices $\lambda$ and $\lambda/(\lambda-1)$ , it follows that

$p_{1}(s, t)|x_{1}(s, t)|^{\lambda}\leq\frac{1}{2^{\lambda}}p_{1}(s, t)\left(\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t} (x_{1})_{\alpha^{2}}(s, t)\right|d_{\alpha}sd_{\alpha}t \right)^{\lambda}\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\begin{align} \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \leq\frac{1}{2^{\lambda}}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}(st)^{\alpha(\lambda-1)}p_{1}(s, t)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t, \end{align}$

(3.7)

Similarly

$\begin{align} p_{2}(s, t)|x_{2}(s, t)|^{\lambda}\leq\frac{1}{2^{\lambda}}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}(st)^{\alpha(\lambda-1)}p_{2}(s, t)\int_{0}^{a}\int_{0}^{b} \left|\frac{\partial^{2}}{\partial s\partial t}(x_{2})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t, \end{align}$

(3.8)

Taking the sum of (3.7) and (3.8) and $\alpha$ -integrating the resulting inequalities over $t$ from $0$ to $b$ first and then over $s$ from $0$ to $a$ , we obtain

$\int_{0}^{a}\int_{0}^{b}\left(p_{1}(s, t)|x_{1}(s, t)|^{\lambda}+p_{2}(s, t)|x_{2}(s, t)|^{\lambda}\right)d_{\alpha}s d_{\alpha}t\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\begin{eqnarray*} &\leq&\frac{1}{2^{\lambda}}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\Bigg\{\int_{0}^{a}\int_{0}^{b}\left((st)^{\alpha(\lambda-1)}p_{1}(s, t) \int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)d_{\alpha}sd_{\alpha}t\\ &+&\int_{0}^{a}\int_{0}^{b}\left((st)^{\alpha(\lambda-1)}p_{2}(s, t)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{2})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\right)d_{\alpha}sd_{\alpha}t\Bigg\}\\ & = &\frac{1}{2^{\lambda}}\left(\frac{1}{\alpha^{2}}\right)^{\lambda-1}\Bigg[\left(\int_{0}^{a}\int_{0}^{b}(st)^{\alpha(\lambda-1)}p_{1}(s, t) d_{\alpha}sd_{\alpha}t\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{1})_{\alpha^{2}}(s, t)\right|^{\lambda} d_{\alpha}sd_{\alpha}t\\ &+&\left(\int_{0}^{a}\int_{0}^{b}(st)^{\alpha(\lambda-1)}p_{2}(s, t)d_{\alpha}sd_{\alpha}t\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t}(x_{2})_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\Bigg]. \end{eqnarray*}$

Remark 3.2 Taking for $x_{1}(s, t) = x_{2}(s, t) = x(s, t)$ and $p_{1}(s, t) = p_{2}(s, t) = p(s, t)$ in (3.6), (3.6) changes to the following inequality.

$\int_{0}^{a}\int_{0}^{b}p(s, t)|x(s, t)|^{\lambda}d_{\alpha}sd_{\alpha}t\leq\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\begin{align} \times\left(\int_{0}^{a}\int_{0}^{b}(st)^{\alpha(\lambda-1)}p(s, t) d_{\alpha}sd_{\alpha}t\right) \int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t} (x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t. \end{align}$

(3.9)

Putting $\alpha = 1$ in (3.9), we have

$\begin{align} \int_{0}^{a}\int_{0}^{b}p(s, t)|x(s, t)|^{\lambda}dsdt\leq\frac{1}{2^{\lambda}}\left(\int_{0}^{a}\int_{0}^{b}(st)^{\lambda-1}p(s, t) dsdt\right)\int_{0}^{a}\int_{0}^{b}\left|\frac{\partial^{2}}{\partial s\partial t} x(s, t)\right|^{\lambda}dsdt. \end{align}$

(3.10)

Let $x(s, t)$ reduce to $s(t)$ and with suitable modifications, and $\lambda = 1$ , (2.10) becomes the following result.

$\begin{align} \int_{0}^{a}p(t)|x(t)|dt\leq\frac{1}{2}\left(\int_{0}^{a}p(t)dt\right)\int_{0}^{a}\left|x'(t)\right|dt. \end{align}$

(3.11)

This is just a new inequality established by Agarwal and Pang ^[4]. For $\lambda = 2$ the inequality (3.11) has appear in the work of Traple ^[14], Pachpatte ^[13] proved it for $\lambda = 2m$ ( $m\geq 1$ an integer).

Remark 3.3 Let $x_{j}(s, t)$ reduce to $x_{j}(t)$ ( $j = 1, 2$ ) and $p_{j}(s, t)$ reduce to $p_{j}(t)$ ( $j = 1, 2$ ) with suitable modifications, (3.6) becomes the following interesting result.

$\int_{0}^{a}\left(p_{1}(t)|x_{1}(t)|^{\lambda}+p_{2}(t)|x_{2}(t)|^{\lambda}\right)d_{\alpha}t\leq\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\Bigg[\left(\int_{0}^{a}t^{\alpha(\lambda-1)}p_{1}(t)d_{\alpha}t\right)\int_{0}^{a}\left|{\cal D }_{\alpha}(x'_{1})(t)\right|^{\lambda} d_{\alpha}t$

$\begin{align} \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; +\left(\int_{0}^{a}t^{\alpha(\lambda-1)}p_{2}(t)d_{\alpha}t\right)\int_{0}^{a}\left|{\cal D}_{\alpha}(x'_{2})(t)\right|^{\lambda}d_{\alpha}t\Bigg]. \end{align}$

(3.12)

Putting $\lambda = 1$ and $\alpha = 1$ in (3.12), we have the following interesting result.

$\int_{0}^{a}\left(p_{1}(t)|x_{1}(t)|+p_{2}(t)|x_{2}(t)|\right)dt\leq\frac{1}{2}\Bigg(\int_{0}^{a}p_{1}(t)dt\int_{0}^{a}\left|x'_{1}(t)\right| dt+\int_{0}^{a}p_{2}(t)dt\int_{0}^{a}\left|x'_{2}(t)\right|dt\Bigg).$

Finally, we give an example to verify the effectiveness of the new inequalities. Estimate the following double integrals:

$\int_{0}^{1}\int_{0}^{1}\Big[st(s-1)(t-1)\Big]^{\lambda}dsdt,$

where $\lambda\geq 1$ .

Let $x_{1}(s,t)=x_{2}(s,t)= x(s, t) = st(s-1)(t-1)$ , $p_{1}(s,t)=p_{2}(s,t)= p(s, t) = (st)^{1-\alpha}$ , $a = b = 1$ and $0 < \alpha\leq 1$ , and by using Theorem 3.2, we obtain

$\int_{0}^{1}\int_{0}^{1}\Big[st(s-1)(t-1)\Big]^{\lambda}dsdt\; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \; \;$

$\begin{eqnarray*} & = &\int_{0}^{1}\int_{0}^{1}p(s, t) \left|x(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\\ &\leq&\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\left(\int_{0}^{1}\int_{0}^{1}(st)^{\alpha(\lambda-1)}p(s, t) d_{\alpha}sd_{\alpha}t\right) \int_{0}^{1}\int_{0}^{1}\left|\frac{\partial^{2}}{\partial s\partial t} (x)_{\alpha^{2}}(s, t)\right|^{\lambda}d_{\alpha}sd_{\alpha}t\\ & = &\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\left(\frac{1}{\alpha(\lambda-1)+1}\right)^{2} \int_{0}^{1}\int_{0}^{1}\Big[(2s-1)(2t-1)\Big]^{\lambda}(st)^{\alpha-1}dsdt\\ & = &\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\left(\frac{1}{\alpha(\lambda-1)+1}\right)^{2} \left(\frac{1}{2^{\alpha-1}}\int_{-1}^{1}t^{\lambda}\frac{1}{(t+1)^{1-\alpha}}dt\right)^{2}\\ &\leq&\frac{1}{2^{\lambda}}\left(\frac{1} {\alpha^{2}}\right)^{\lambda-1}\left(\frac{1}{\alpha(\lambda-1)+1}\right)^{2} \left(\frac{1}{2^{\alpha-1}}\frac{2^{\alpha}}{\alpha}\right)^{2}\\ & = &\frac{2^{2-\lambda}}{\alpha^{2\lambda}\left(\alpha(\lambda-1)+1\right)^{2}}. \end{eqnarray*}$

4. Conclusions

We have introduced a general version of Opial-Wirtinger's type integral inequality for the Katugampola partial derivatives. The established results are generalization of some existing Opial type integral inequalities in the previous published studies. For further investigations we propose to consider the Opial-Wirtinger's type inequalities for other partial derivatives.

Acknowledgments

I would like to thank that research is supported by National Natural Science Foundation of China(11471334, 10971205).

Conflict of interest

The author declares no conflicts of interest.

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