Differentiation of rat embryonic stem cells into functional cardiomyocytes

Rats(Rattus norvegicus) have many advantages over mice in scientific studies,for example, they are more relevant to human in physiological and pharmacological responses.Therefore,rats are broadly used in experimental studies.The recent breakthrough in the generation of rat embryonic stem cells(rESCs) opens the door to application of gene targeting to create models for the study of human diseases.In addition,the in vitro differentiation of rESCs into derivatives of three germ lines will serve as a powerful tool and resource for the investigation of mammalian development,cell function, tissue repair,and drug discovery.However, the distinct culture condition and signal inhibitor-depended maintenance of rESCs stand as a considerable challenge for its in vitro differentiation.To address it,we investigated whether rESCs are capable of forming terminal differentiated cardiomyocytes. We found that the embryoid bodies(EBs)-based method used in mouse ESC(mESC) differentiation failed to work in the cultivation of rESCs.We then modified the differentiation protocol and successfully developed an in vitro differentiation system to differentiate rESCs into three embryonic germ layers.By using this method,the rESCs form spontaneous beating cardiomyocytes with the properties similar to those derived from fetal rat hearts and mESCs.This unique cellular system will provide a new approach to study the early development and cardiac function as well as to perform pharmacological test and cell therapy study(Grants:the State Major Research Program of China(2009ZX09503-024,2010CB945603) and CAS(XDA01030000).

A Numerical Method for Solving Ill-Conditioned Equation Systems Arising from Radial Basis Functions

Continuously differentiable radial basis functions (C∞-RBFs), while being theoretically exponentially convergent are considered impractical computationally because the coefficient matrices are full and can become very ill- conditioned. Similarly, the Hilbert and Vandermonde have full matrices and become ill-conditioned. The difference between a coefficient matrix generated by C∞-RBFs for partial differential or integral equations and Hilbert and Vandermonde systems is that C∞-RBFs are very sensitive to small changes in the adjustable parameters. These parameters affect the condition number and solution accuracy. The error terrain has many local and global maxima and minima. To find stable and accurate numerical solutions for full linear equation systems, this study proposes a hybrid combination of block Gaussian elimination (BGE) combined with arbitrary precision arithmetic (APA) to minimize the accumulation of rounding errors. In the future, this algorithm can execute faster using preconditioners and implemented on massively parallel computers.

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus

The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin(red in RCC,brownish-yellow in4nRR).To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR,we performed transcriptome profiling and molecular functional verification in RCC and 4nRR.Results revealed that scarb1,associated with carotenoid metabolism,underwent significant down-regulation in 4nRR.Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration.Subsequently,we identified four divergent scarb1 homeologs in 4nRR:two original scarb1 homeologs from RCC and two duplicated ones.Notably,three of these homeologs possessed two highly conserved alleles,exhibiting biased and allelespecific expression in the skin.Remarkably,after precise editing of both the original and duplicated scarb1homeologs and/or alleles,4nRR individuals,whether singly or multiply mutated,displayed a transition from brownishyellow skin to a cyan-gray phenotype.Concurrently,the proportional areas of the cyan-gray regions displayed a gene-dose correlation.These findings illustrate the subfunctionalization of duplicated scarb1,with all scarb1genes synergistically and equally contributing to the pigmentation of 4nRR.This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploidfish,substantiallyenrichingour understanding of coloration formation and change within this group of organisms.

Existence of Periodic Solutions for Generalized Liénard-Typed Functional Differential Equations

The existence of periodic solutions for a kind of generalized Liénard typed functional differential equation is studied. By means of the continuation theorem of coincidence degree theory, existence criteria are established for the existence of periodic solutions and some previous results are extended.

The Global Solutions of Impulsive Retarded Functional Differential Equations

In this paper, we present some results on the existence of the golbal solutions of nonlinear impulsive retarded functional differential equations.

EXISTENCE OF POSITIVE PERIODIC SOLUTIONS FOR NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATIONS WITH DEVIATING ARGUMENTS

By means of an abstract continuation theorem, the existence criteria are established for the positive periodic solutions of a neutral functional differential equation d N d t=N(t)[a(t)-β(t)N(t)-b(t)N(t-σ(t))-c(t)N′(t-τ(t))].

RAZUMIKHIN-TYPE THEOREM FOR NEUTRAL STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS WITH UNBOUNDED DELAY

This paper establishes the Razumikhin-type theorem on stability for neutral stochastic functional differential equations with unbounded delay. To overcome difficulties from unbounded delay, we develop several different techniques to investigate stability. To show our idea clearly, we examine neutral stochastic delay differential equations with unbounded delay and linear neutral stochastic Volterra unbounded-delay-integro-differential equations.

EXISTENCE OF POSITIVE SOLUTIONS FOR p-LAPLACIAN SINGULAR BOUNDARY VALUE PROBLEMS OF FUNCTIONAL DIFFERENTIAL EQUATION

In this paper,the boundary value problems of p-Laplacian functional differential equation are studied.By using a fixed point theorem in cones,some criteria for the existence of positive solutions are given.

A Boundary Value Problem for Second Order Functional Differential Equations with Impulses

Aim To investigate the boundary value problem for second order functional differentiai equations with impulses. Methods The fixed point principle was used to establish our results. Results and Conclusion The results of the esistence, the uniqueness and the continuous dependence on aprameter of soiutions of the boundary value problems for second order functional differential equations with impulses are obtained.

Periodic boundary value problem for the first order functional differential equations with impulses

This paper is concerned with the existence and approximation of solutions for a class of first order impulsive functional differential equations with periodic boundary value conditions. A new comparison result is presented and the previous results are extended.

Periodic Boundary Value Problem for Functional Differential Equations with Impulses

Aim To investigate the periodic boundary value problem for functional differential equations with impulses. Methods The method of upper and lower solutions and the monotone iterative technique were used to establish our results. Results and Conclusion The results of the existence of maximal and minimal solutions of the periodic boundary value problem for functional differential equations with impulses are obtained.

THE EXISTENCE OF PERIODIC SOLUTIONS FOR A CLASS OF FUNCTIONAL DIFFERENTIAL EQUATIONS AND THEIR APPLICATION

In this paper. four sufficiency theorems of existence of periodic solutions for aclass of retarded functional differential equations are given. The result of thesetheorems is better than the well-known Yoshizawa’s periodic solution theorem. Anexample of application is given at the end.

HOMOCLINIC SOLUTIONS FOR A CLASS OF SECOND ORDER NEUTRAL FUNCTIONAL DIFFERENTIAL SYSTEMS

By means of an extension of Mawhin＇s continuation theorem and some analysis methods, the existence of a set with 2kT-periodic solutions for a class of second order neutral functional differential systems is studied, and then the homoclinic solutions are obtained as the limit points of a certain subsequence of the above set.

THIRD-ORDER DIFFERENTIAL SUBORDINATION RESULTS FOR ANALYTIC FUNCTIONS INVOLVING THE GENERALIZED BESSEL FUNCTIONS

In the present paper, we derive some third-order differential subordination results for analytic functions in the open unit disk, using the operator Bcκf by means of normalized form of the generalized Bessel functions of the first kind, which is defined as z（Bκ＋1^c f（z））′= κBκ^c f（z）-（κ- 1）Bκ＋1^c f（z）,where b, c, p ∈ C and κ = p ＋（b ＋ 1）/2 ∈ C ／ Z0^-（Z0^-= {0,-1,-2, … }）. The results are obtained by considering suitable classes of admissible functions. Various known or new special cases of our main results are also pointed out.

RAZUMIKHIN-TYPE THEOREMS OF NEUTRAL STOCHASTIC FUNCTIONAL DIFFERENTIAL EQUATIONS

The stability of stochastic functional differential equation with Markovian switching was studied by several authors,but there was almost no work on the stability of the neutral stochastic functional differential equations with Markovian switching.The aim of this article is to close this gap.The authors establish Razumikhin-type theorem of the neutral stochastic functional differential equations with Markovian switching,and those without Markovian switching.

ASYMPTOTIC PROPERTIES OF FUNCTIONAL DIFFERENTIAL EQUATIONS IN BANACH SPACES

The paper is devoted to the asymptotic properties of functional differential equations in Banach spaces.The criteria of the invariant and attracting sets are obtained.Particularly, the sufficient condition of asymptotic stability of the equilibrium point is given as the system has an equilibrium point.Several examples are also worked out to demonstrate the validity of the results.

SIMULTANEOUSE APPROXIMATION TO A DIFFERENTIABLE FUNCTION AND ITS DERIVATIVES BY LAGRANGE INTERPOLATING POLYNOMIALS

This paper establishes the following pointwise result for simultancous Lagrange imterpolating approxima- tion:,then |f^(k)(x)-P_n^(k)(f,x)|=O(1)△_n^(q-k)(x)ω where P_n(f,x)is the Lagrange interpolating potynomial of deereeon the nodes X_nUY_n(see the definition of the next).

Asymptotic stability for impulsive functional differential equations

In this paper, we investigate the stability of a class of impulsive functional differential equations by using Lyapunov functional and Jensen＇s inequality. Some new stability theorems are obtained. Examples are given to demonstrate the advantage of the obtained results.

PERIODIC SOLUTIONS OF THIRD-ORDER FUNCTIONAL DIFFERENTIAL EQUATIONS WITH VARIABLE COEFFICIENTS

The sufficient condition for the existence of2 π- periodic solutions of the following third- order functional differential equations with variable coefficients a(t) x (t) +bx″2 k- 1(t) +cx′2 k- 1(t) + 2 k- 1 i=1 cixi(t) +g(x(t-τ) ) =p(t) =p(t+2π) is obtained.The approach is based on the abstract continuation theorem from Mawhin and the a- priori estimate of periodic solutions

On Stability of Solutions of a Certain Fourth-Order Functional Differential Equations

Using a Razumikhin-type theorem,we obtain sufficient conditions for the global asymptotic stability of the zero solution of a certain fourth order functional differential equations.The result generalizes the well known results.