摘要： Minimal residual disease (MRD) is an important emerging clinical end point in chronic lymphocytic leukemia (CLL). The objective of this research was to develop an integrated mechanistic model to evaluate the impact of venetoclax-rituximab combination therapy on MRD kinetics. Using data from 435 patients with relapsed or refractory CLL, an integrated model was developed and validated that accounted for venetoclax dosing and pharmacokinetics, rituximab treatment, absolute lymphocyte count, and blood and bone marrow (BM) MRD data. Simulations of venetoclax-rituximab (six cycles) combination predicted the proportion (90% confidence interval) of patients with BM MRD below 10(-4)to be 57% (54-61%) and 63% (59-67%) at 12 and 24 months of treatment, respectively. Continued venetoclax treatment to 48 months only increased the predicted rate of negative BM MRD to 66% (63-70%). These results indicate that treatment with venetoclax-rituximab combination for a finite 2-year period would nearly maximize the rate of negative BM MRD (< 10(-4)). Preliminary clinical data agree with these predictions and more long-term follow-up data are awaited to confirm the same.

关键词： Glass  

摘要： This work focused on investigating the mechanical, optical features and gamma-ray shielding parameters of different five glasses coded as W1, W2, W3, W4, and W5 based on 0.8[xBaO (1-x)MgO]-0.2WO(3)-2TeO(2):x = 0, 0.3, 0.5, 0.7, and 1 mol%. According to Makishima-Mackenzie's model, the total ionic packing density (V-t) and the total dissociation energy (G(t)) for the investigated glasses were computed. Then, the main mechanical features (elastic moduli and Poisson's ratio) haven been calculated. The optical features such as optical electronegativity (chi*) and linear dielectric susceptibility (chi((1))) and other related parameters for the W1-W5 glasses were also computed. Utilizing the newly Phy-X/PSD program, mass attenuation coefficient (MAC) has been computed. Based on MAC values, linear attenuation coefficient (LAC), half value layer (HVL), mean free path (MFP), and effective atomic number (Z(eff)) as radiation shielding parameters were evaluated. Results revealed that the (V-t) increased from 0.39 to 0.49, while (G(t)) decreased from 84.94 x 10(6) to 45.33 x 10(6) (KJ/m(3)) for W1 to W5 glasses. The elastic properties varied from 76.21 to 44.32 GPa for Young's modulus, from 29.25 to 18.23 GPa for shear modulus, from 32.29 to 26.00 GPa for bulk modulus, from 70.91 to 50.30 GPa for longitudinal modulus, and from 0.15 to 0.22 for Poisson's ratio. The value of chi* changed from 0.84 to 0.41, while chi((1)) changed from 0.62 to 0.36. HVL and MFP values are in the ascending order of W1 > W2 > W3 > W4 > W5. Therefore, the W5 glass (contains the highest concentration of BaO) has the best radiation shielding efficiency among the other samples W1-W4. Correlations between shielding features (MAC and HVL) at different photon energy are estimated, where MAC and HVL have been improved by increasing the BaO in W1-W5 glasses.

关键词： Quasiperiodic oscillator   Quasiperiodic Mathieu   Quasiperiodic variance   Sub-harmonic resonance   Semi classical-quantum dynamics  

摘要： Quasiperiodically driven quantum parametric oscillators have been the subject of several recent investigations. Here we show that for such oscillators, the instability zones of the mean position and variance (alternatively the mean energy) for a time developing wave packet are identical for the strongest resonance in the three-dimensional parameter space of the quasiperiodic modulation as it is for the two-dimensional parameter space of the periodic modulations. (C) 2020 Elsevier B.V. All rights reserved.

关键词： Flexible mechanical metamaterials   Nonlinear dynamics   Cnoidal waves  

摘要： Flexible mechanical metamaterials have been recently shown to support a rich nonlinear dynamic response. In particular, it has been demonstrated that the behavior of rotating-square architected systems in the continuum limit can be described by nonlinear Klein-Gordon equations. Here, we report on a general class of solutions of these nonlinear Klein-Gordon equations, namely cnoidal waves based on the Jacobi elliptic functions sn, cn and dn. By analyzing theoretically and numerically their validity and stability in the design- and wave-parameter space, we show that these cnoidal wave solutions extend from linear waves (or phonons) to solitons, while covering also a wide family of nonlinear periodic waves. The presented results thus reunite under the same framework different concepts of linear and non-linear waves and offer a fertile ground for extending the range of possible control strategies for nonlinear elastic waves and vibrations.

关键词： Rangeland rehabilitation   Land degradation   Surface runoff   Soil moisture   Erosion  

摘要： Overexploitation and climate change accelerate the degradation of Jordan's arid rangelands. Uncovered and crusted soils increase runoff and erosion and hinder the emergence of the native vegetation. Micro water harvesting combined with shrub-seedling plantation have been widely applied to reverse land degradation trends. However, consequential soil water and vegetation dynamics have been rarely assessed, which constrains further out-scaling of the rehabilitation practice to complex environments. In Jordan, an experiment was set up to study the linkages between local rainfall characteristics, soil moisture and the development of out-planted shrub seedlings. Soil moisture was recorded at approximately weekly time-interval during the rainy and dry season 2017/2018 using a manually operated soil water sensor. Transect monitoring was pursued up and down the slope across four micro water harvesting pits and the interspaces. Data confirmed a significant soil moisture increase inside the pits bridging intra-seasonal dry spells and soil water potentially deep-percolated into the karstic bedrock underneath. The study found that the out-planted shrubs' stem diameter and height predominantly increased during post rainy season, when the interspaces dried up while the pits continued providing moisture. The results are promising and contribute to integrated research towards halting land degradation and sustainable agro-pastoral development.

关键词： Compound "supHopf/homoclinic-fold/supHopf" bursting   Compound "supHopf/supHopf-fold/supHopf" bursting   Fast-slow analysis   Bifurcations   Transition of bursting  

摘要： This paper aims to report complex bursting dynamics in a parametrically and externally excited mechanical system. Typically, two compound bursting patterns, i.e., bursting of "supHopf/homoclinic-fold/supHopf" type and bursting of "supHopf/supHopf-fold/supHopf" type, composed of two different clusters during each period of bursting, can be observed in this system. To begin with, the generation of each of the two clusters in compound bursting of "supHopf/homoclinic-fold/supHopf" type is investigated by the fast-slow analysis. Then, a two-parameter bifurcation diagram is plotted to investigate the transition of the compound bursting. We show that there are two originally disunited active areas, which may inosculate as a whole by homoclinic bifurcations if the system parameter varies properly. Based on this, a different type of compound bursting, i.e., bursting of "supHopf/supHopf-fold/supHopf" type, is revealed. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： Ordinary differential equations   Numerical integration   Energy-preserving methods   MB4 method   Nonlinear Schrodinger equation   Parallel computing  

摘要： In simulating physical systems, conservation of the total energy is often essential, especially when energy conversion between different forms of energy occurs frequently. Recently, a new fourth order energy-preserving integrator named MB4 was proposed based on the so-called continuous stage Runge-Kutta methods (Miyatake and Butcher in SIAM J Numer Anal 54(3):1993-2013, 2016). A salient feature of this method is that it is parallelizable, which makes its computational time for one time step comparable to that of second order methods. In this paper, we illustrate how to apply the MB4 method to a concrete ordinary differential equation using the nonlinear Schrodinger-type equation on a two-dimensional grid as an example. This system is a prototypical model of two-dimensional disordered organic material and is difficult to solve with standard methods like the classical Runge-Kutta methods due to the nonlinearity and the delta-function like potential coming from defects. Numerical tests show that the method can solve the equation stably and preserves the total energy to 16-digit accuracy throughout the simulation. It is also shown that parallelization of the method yields up to 2.8 times speedup using 3 computational nodes.

关键词： Aluminum alloys   Precipitation kinetics   Atom-probe tomography   Elevated-temperature  

摘要： A micro-addition (0.025 at.%) of slow-diffusing W to an Al-0.26Mn-0.11Mo-0.11Si-0.08Zr-0.02Sc-0.01Er (at.%) alloy accelerates L1(2)-Al-3(Zr,Sc) precipitation but retards alpha-Al(Mn,Mo)Si precipitation. The W micro-addition increases the peak-microhardness of the alloy during isothermal aging but does not improve the coarsening resistance and creep resistance.

关键词： Hydrogenated defective graphene   Exothermic H-2 desorption   Density functional theory   Molecular dynamics simulations   Activation barrier   Tensile strength  

摘要： A combined density functional theory and molecular dynamics approach is employed to study modifications of graphene at atomistic level for better H-2 storage. The study reveals H-2 desorption from hydrogenated defective graphene structure, V-222, to be exothermic. H-2 adsorption and desorption processes are found to be more reversible for V-222 as compared to pristine graphene. Our study shows that V-222 undergoes brittle fracture under tensile loading similar to the case of pristine graphene. The tensile strength of V-222 shows slight reduction with respect to their pristine counterpart, which is attributed to the transition of sp(2) to sp(3)-like hybridization. The study also shows that the V-222 structure is mechanically more stable than the defective graphene structure without chemically adsorbed hydrogen atoms. The current fundamental study, thus, reveals the efficient recovery mechanism of adsorbed hydrogen from V-222 and paves the way for the engineering of structural defects in graphene for H-2 storage. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of Hydrogen Energy Publications LLC.

关键词： Transition states   Chemical reactions   Solvents   Ab initio molecular dynamics   Post-translational modification  

摘要： We report a computational approach to evaluate the reaction mechanisms of glycosylation using ab initio molecular dynamics (AIMD) simulations in explicit solvent. The reaction pathways are simulated via free energy calculations based on metadynamics and trajectory simulations using Born-Oppenheimer molecular dynamics. We applied this approach to investigate the mechanisms of the glycosylation of glucosyl alpha-trichloroacetimidate with three acceptors (EtOH, i-PrOH, and t-BuOH) in three solvents (ACN, DCM, and MTBE). The reactants and the solvents are treated explicitly using density functional theory. We show that the profile of the free energy surface, the synchronicity of the transition state structure, and the time gap between leaving group dissociation and nucleophile association can be used as three complementary indicators to describe the glycosylation mechanism within the S(N)1/S(N)2 continuum for a given reaction. This approach provides a reliable means to rationalize and predict reaction mechanisms and to estimate lifetimes of oxocarbenium intermediates and their dependence on the glycosyl donor, acceptor, and solvent environment.