A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor

A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18) column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acid in water) and mobile phase B(0.1% formic acid in acetonitrile), at a flow rate of 0.4 m L/min. Ceritinib and the internal standard([^(13)C_6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation(LLOQ) was 1 n M of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 n M in plasma. The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method( o15%).The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.

New shakedown criterion and permanent deformation properties of unbound granular materials

Unbound granular material specifications for road pavements in Australia are primarily based on physical material specification rather than mechanical characterisation. This simplified approach does not reflect the actual material performance under repeated dynamic traffic loads. There is a little information available on the influence of the local crushed rock properties and compacted layer properties on permanent deformation (PD). This study aims to characterise the local unbound granular materials in Victoria according to their PD behaviour under repeated loads and to develop a suitable shakedown criterion that could describe the PD of the tested materials to simplify the flexible pavement design. Repeated-load triaxial tests were conducted over several samples with a range of moisture contents, gradations, densities, and stress conditions. The laboratory test results showed that PD behaviour was influenced by several factors. In addition, the tested subbase-specified unbound granular materials reflect high PD resistance that is almost equivalent to basequality unbound granular materials. This may indicate that current requirements for the subbase-quality unbound granular materials are over-prescribe. Moreover, as the existing shakedown criterion was not applicable for the multi-stage repeated-load triaxial test and the local tested materials, a new shakedown criterion and new boundaries are proposed based on the PD behaviour. In the proposed criterion, the shakedown ranges are identified based on the curve angle of the PD vs. logarithm of the number of loading cycles, and this new criterion was validated using several materials from existing literature. The local tested base and subbase materials can be assigned as Range A when PD\1%, Range B when 1%\PD\3%, and Range C when PD[3%. The proposed criterion could provide a useful and quick approach to assess the PD of the unbound granular materials with both single and multistages of stresses.

Effect of vertical stress rest period on deformation behaviour of unbound granular materials:Experimental and numerical investigations

Repeated load triaxial test is used to assess the deformation behaviour of unbound granular materials(UGMs) in flexible road pavements. Repeated load pulse characteristics(i.e. shape, loading period and rest period) are the stress configurations used in the experimental set-up to simulate the passing axle loads. Some researchers and standard testing protocols suggest a rest period of varying durations after a loading phase. A thorough review of existing literature and practises has revealed that there is no agreement about the effect of the rest period of vertical stress pulse on the deformation behaviour of the UGMs. Therefore,the main objective of this study is to investigate the effect of repeated stress rest period on the deformation behaviour of UGMs experimentally. Experiments are conducted, both with and without rest period, using basalt and granite crushed rocks from Victoria, Australia. Furthermore, in order to gain insight into the effect of the rest period, finite element modelling is also developed. Both the experimental and modelling results show that the rest period has a noticeable effect on both resilient and permanent deformation behaviours of UGMs. It is, therefore, recommended to take extra precautions while adopting a particular standard testing protocol and to supplement the results by additional tests with different loading configurations.

Random Attractors for Stochastic Reaction-Diffusion Equations with Distribution Derivatives on Unbounded Domains

In this paper, we prove the existence of random attractors for a stochastic reaction-diffusion equation with distribution derivatives on unbounded domains. The nonlinearity is dissipative for large values of the state and the stochastic nature of the equation appears spatially distributed temporal white noise. The stochastic reaction-diffusion equation is recast as a continuous random dynamical system and asymptotic compactness for this demonstrated by using uniform estimates far-field values of solutions. The results are new and appear to be optimal.

ATTRACTORS FOR THE GINZBURG-LANDAU-BBM EQUATIONS IN AN UNBOUNDED DOMAIN

By the interpolating inequality and a priori estimates in the weighted space,the existence of the global solutions for the Ginzburg-Landau equation coupled with the BBM equation in an unbounded domain is considered, and the existence of the maximal attractor is obtained.

INFINITE ELEMENT METHOD FOR PROBLEMS ON UNBOUNDED AND MULTIPLY CONNECTED DOMAINS

The author studies the infinite element method for the boundary value problems of second order elliptic equations on unbounded and multiply connected domains. The author makes a partition of the domain into infinite number of elements. Without dividing the domain, as usual, into a bounded one and an exterior one, he derives an initial value problem of an ordinary differential equation for the combined stiffness matrix, then obtains the approximate solution with a small amount of computer work. Numerical examples are given.

Global Topological Linearization with Unbounded Nonlinear Term

In 1960s, Hartman and Grobman pointed out that if all eigenvalues of a matrix A have no zero real part and f(x) is small Lipchitzian, then x′=Ax+f(x) can be locally linearized on a neighborhood of the origin. Later, the above result was generalized to global under the condition that f(x) is a bounded function. In this paper, we delete the condition that f(x) is a bounded function, and prove that if f(x) has suitable structure, then x′=Ax+f(x) can be linearized.

ON SOLUTIONS OF BACKWARD STOCHASTIC DIFFERENTIAL EQUATIONS WITH JUMPS,WITH UNBOUNDED STOPPING TIMES AS TERMINAL AND WITH NON-LIPSCHITZ COEFFICIENTS,AND PROBABILISTIC INTERPRETATION OF QUASI-LINEAR ELLIPTIC TYPE INTEGRO-DIFFERENTIAL EQUATIO

The existence and uniqueness of solutions to backward stochastic differential equations with jumps and with unbounded stopping time as terminal under the non_Lipschitz condition are obtained. The convergence of solutions and the continuous dependence of solutions on parameters are also derived. Then the probabilistic interpretation of solutions to some kinds of quasi_linear elliptic type integro_differential equations is obtained.

Homotopy Continuous Method for Weak Efficient Solution of Multiobjective Optimization Problem with Feasible Set Unbounded Condition

In this paper, we propose a homotopy continuous method (HCM) for solving a weak efficient solution of multiobjective optimization problem (MOP) with feasible set unbounded condition, which is arising in Economical Distributions, Engineering Decisions, Resource Allocations and other field of mathematical economics and engineering problems. Under the suitable assumption, it is proved to globally converge to a weak efficient solution of (MOP), if its x-branch has no weak infinite solution.

On the Stable Method Computing Values of Unbounded Operators

Unbounded operators can transform arbitrarily small vectors into arbitrarily large vectors—a phenomenon known as instability. Stabilization methods strive to approximate a value of an unbounded operator by applying a family of bounded operators to rough approximate data that do not necessarily lie within the domain of unbounded operator. In this paper we shall be concerned with the stable method of computing values of unbounded operators having perturbations and the stability is established for this method.

On the Method of Multiplier-enlargement and Approximation of Unbounded Continuous Functions

By combining the classical appropriate functions “1, x, x 2” with the method of multiplier enlargement, this paper establishes a theorem to approximate any unbounded continuous functions with modified positive linear operators. As an example, Hermite Fejér interpolation polynomial operators are analysed and studied, and a general conclusion is obtained.

Error Analysis of ERM Algorithm with Unbounded and Non-Identical Sampling

A standard assumption in the literature of learning theory is the samples which are drawn independently from an identical distribution with a uniform bounded output. This excludes the common case with Gaussian distribution. In this paper we extend these assumptions to a general case. To be precise, samples are drawn from a sequence of unbounded and non-identical probability distributions. By drift error analysis and Bennett inequality for the unbounded random variables, we derive a satisfactory learning rate for the ERM algorithm.

THE EXISTENCE OF INFINITELY MANY SO UTIONS OF QUASILINEAR PARTIAL DIFFERENTIAL EQUATIONS IN UNBOUNDED DOMAINS

In this paper, we use the concentration-compactness principle together with the Mountain Pass Lemma to get the existence of nontrivial solutions and the existence of infinitely many solutions of the problem need not be compact operators from E to R~1.

Neural network-based model for prediction of permanent deformation of unbound granular materials

Several available mechanistic-empirical pavement design methods fail to include predictive model for permanent deformation(PD)of unbound granular materials(UGMs),which make these methods more conservative.In addition,there are limited regression models capable of predicting the PD under multistress levels,and these models have regression limitations and generally fail to cover the complexity of UGM behaviour.Recent researches are focused on using new methods of computational intelligence systems to address the problems,such as artificial neural network(ANN).In this context,we aim to develop an artificial neural model to predict the PD of UGMs exposed to repeated loads.Extensive repeated load triaxial tests(RLTTs)were conducted on base and subbase materials locally available in Victoria,Australia to investigate the PD properties of the tested materials and to prepare the database of the neural networks.Specimens were prepared over different moisture contents and gradations to cover a wide testing matrix.The ANN model consists of one input layer with five neurons,one hidden layer with twelve neurons,and one output layer with one neuron.The five inputs were the number of load cycles,deviatoric stress,moisture content,coefficient of uniformity,and coefficient of curvature.The sensitivity analysis showed that the most important indicator that impacts PD is the number of load cycles with influence factor of 41%.It shows that the ANN method is rapid and efficient to predict the PD,which could be implemented in the Austroads pavement design method.

ON NONLINEAR HYPERBOLIC EQUATION IN UNBOUNDED DOMAIN

The following nonlinear hyperbolic equation is discussed in this paper:where A= -? + Iandx∈Rn. The model comes from the transverse deflection equation of an extensible beam. We prove that there exists a unique local solution of the above equation as M depends on x.

BOUNDARY VALUE PROBLEMS FOR FULLY NONLINEAR UNIFORMLY ELLIPTIC EQUATIONS OF SECOND IN UNBOUNDED DOMAINS

We consider fully nonlinear equations of the formF（z,u,Du,D2u） = F（x,y,u,uz,uy,uzz,uzy,uyy） = 0 （1）in unbounded open subset G = R2\Ωof the plane R2,where F is a real continuous function on U = G×R×R2×R3 and Ω= Ωi,Ωi is a simply connected region （i=1,2,"",N） . We assume the function F hascontinuous partial der ivatives Fuzz, Fuzy, Fuyy. on U.For a real function r C（ G） a real function u（x,y） is called a solution of （1） satisfyingu = r on G,（2）if there exists a constant P0】2 such that u C1 （ ） W2.pLoc0 （G） satisfies （1） almost everywhere and （2）in the common sense.The method for treating the above exterior Dirichlet problem in a given unbounded region is as fol-

Asymptotic Stability of Neutral Differential Equations with Unbounded Delay

Consider the neutral differential equation with positive and negative coefficients and unbounded delay ddt[x(t)-P(t)x(h(t))]+Q(t)x(q(t))-R(t)x(r(t))=0, t≥t 0, where P(t)∈C([t 0, ∞), R), Q(t), R(t)∈C([t 0, ∞), [WTHZ]R +), and h, q, r: [t 0, ∞)→R are continuously differentiable and strictly increasing, h(t)<t, q(t)<t, r(t)<t for all t≥t 0. In this paper, the authors obtain sufficient conditions for the zero solution of this equation with unbounded delay to be uniformly stable as well as asymptotically stable. [WTH1X]

PROBABILITY INEQUALITIES FOR SUMS OF INDEPENDENT UNBOUNDED RANDOM VARIABLES

The tail probability inequalities for the sum of independent unbounded random variables on a probability space (Omega, T, P) were studied and a new method was proposed to treat the sum of independent unbounded random variables by truncating the original probability space (Omega, T, P). The probability exponential inequalities for sums of the results, some independent unbounded random variables were given. As applications of interesting examples were given. The examples show that the method proposed in the paper and the results of the paper are quite useful in the study of the large sample properties of the sums of independent unbounded random variables.

NORM SUMMABILITY OF NRLUND LOGARITHMIC MEANS ON UNBOUNDED VILENKIN GROUPS

The （Noerlund） logarithmic means of the Fourier series is：tnf=1/ln ^n-1∑k=1 Skf/n-k, where ln=^n-1∑k=1 1/k In general, the Fej6r （C, 1） means have better properties than the logarithmic ones. We compare them and show that in the case of some unbounded Vilenkin systems the situation changes.

Approximate Method of Riemann-Hilbert Problem for Elliptic Complex Equations of First Order in Multiply Connected Unbounded Domains

In this article, we discuss the approximate method of solving the Riemann-Hilbert boundary value problem for nonlinear uniformly elliptic complex equation of first order (0.1) with the boundary conditions (0.2) in a multiply connected unbounded domain D, the above boundary value problem will be called Problem A. If the complex Equation (0.1) satisfies the conditions similar to Condition C of (1.1), and the boundary condition (0.2) satisfies the conditions similar to (1.5), then we can obtain approximate solutions of the boundary value problems (0.1) and (0.2). Moreover the error estimates of approximate solutions for the boundary value problem is also given. The boundary value problem possesses many applications in mechanics and physics etc., for instance from (5.114) and (5.115), Chapter VI, [1], we see that Problem A of (0.1) possesses the important application to the shell and elasticity.