Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility

A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor–immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact.     

Euler's fluid equations: Optimal control vs optimization

An optimization method used in image-processing (metamorphosis) is found to imply Euler's equations for incompressible flow of an inviscid fluid, without requiring that the Lagrangian particle labels exactly follow the flow lines of the Eulerian velocity vector field. Thus, an optimal control problem and an optimization problem for incompressible ideal fluid flow both yield the same Euler fluid equations, although their Lagrangian parcel dynamics are different. This is a result of the gauge freedom in the definition of the fluid pressure for an incompressible flow, in combination with the symmetry of fluid dynamics under relabeling of their Lagrangian coordinates. Similar ideas are also illustrated for SO(N) rigid body motion.     

空间桁架结构的优化配置及振动控制研究

为抑制空间柔性桁架结构的低频振动,采用压电杆件进行优化配置实现桁架结构的振动主动控制。建立了空间桁架结构主动压电杆件的机电耦合模型,利用ANSYS前处理功能编制了压电桁架的机电耦合有限元程序。将可控性度量指标与逐步消减法相结合,实现了空间桁架结构主动杆件的优化配置。对结构进行初始位移扰动、正弦激励以及随机激励,并采用最优模态控制算法进行振动抑制仿真分析,对上述方法进行验证且建立振动控制评价指标进行评价。结果表明将可控性度量指标与逐步消减法相结合的方法可有效抑制空间柔性桁架结构的振动。     

Enhancing photothermal cancer therapy by clustering gold nanoparticles into spherical polymeric nanoconstructs

Gold nanoparticles (AuNPs) have been proposed as agents for enhancing photothermal therapy in cancer and cardiovascular diseases. Different geometrical configurations have been used, ranging from spheres to rods and more complex star shapes, to modulate optical and ablating properties. In this work, multiple, ultra-small 6 nm AuNPs are encapsulated into larger spherical polymeric nanoconstructs (SPNs), made out of a poly(lactic acid-co-glycol acid) (PLGA) core stabilized by a superficial lipid-PEG monolayer. The optical and photothermal properties of the resulting nanoconstructs (Au-SPNs) are modulated by varying the initial loading input of AuNPs, ranging between 25 and 150 μg_Au. Au-SPNs exhibit a hydrodynamic diameter varying from ~100 to 180 nm, growing with the gold content, and manifest up to 2-fold increase in thermal energy production per unit mass of gold for an initial input of 100 μg_Au. Au-SPNs are stable under physiological conditions up to 7 days and have direct cytotoxic effect on tumor cells. The superior photothermal performance of Au-SPNs is assessed in vitro on monolayers of breast cancer cells (SUM-159) and tumor spheroids of glioblastoma multiforme cells (U87-MG). The encapsulation of small AuNPs into larger spherical nanoconstructs enhances photothermal ablation and could favor tumor accumulation.     

Optimal vaccination and treatment of an epidemic network model

In this Letter, we firstly propose an epidemic network model incorporating two controls which are vaccination and treatment. For the constant controls, by using Lyapunov function, global stability of the disease-free equilibrium and the endemic equilibrium of the model is investigated. For the non-constant controls, by using the optimal control strategy, we discuss an optimal strategy to minimize the total number of the infected and the cost associated with vaccination and treatment. Table 1 and Figs. 1–5 are presented to show the global stability and the efficiency of this optimal control.     

Optimal response in the Lamb-Oseen vortex

The optimal response in the Lamb-Oseen vortex is studied by considering the harmonically forced problem with frequency ω. High variance levels are sustained in these systems under periodic forcing. In the axisymmetric case n=0, the response is the largest when the input frequency is zero. When considering helical perturbations n=1, large response is excited through resonance mechanism at moderate and large wavelengths. At smaller wavelengths, large response is excited by steady forcing. For perturbations with higher azimuthal wavenumbers |n|>1, the magnitudes of the response are smaller than those for helical modes. For given axial wavenumber and input frequency, the response increases rapidly with Re, which points to the significance of energy growth in high-Reynolds-number practical flows.     

Superconvergence of Mixed Methods for Optimal Control Problems Governed by Parabolic Equations

In this paper, we investigate the superconvergence results for optimal control problems governed by parabolic equations with semi-discrete mixed finite element approximation. We use the lowest order mixed finite element spaces to discrete the state and costate variables while use piecewise constant function to discrete the control variable. Superconvergence estimates for both the state variable and its gradient variable are obtained.     

基于最小稳定过热度的制冷系统变负荷优化控制

通过对采用变频压缩机和电子膨胀阀的变容量制冷系统稳定性的机理分析与实验研究辨识得到了与制冷量相匹配的蒸发器最小稳定过热度,并通过对压缩机频率阶跃变化下制冷系统的特性分析对最小稳定过热度进行了验证。采用基于最小稳定过热度的压缩机频率和电子膨胀阀开度协调控制方法,在制冷系统变负荷工况下进行了试验。结果表明,该方法很好的适应了制冷系统变工况的控制要求,相比常规的定过热度控制,具有跟踪性能良好、动态控制精度高,并能有效的提高制冷系统的变负荷运行时的性能系数(COP)。     

Four-dimensional scheduling for uplink dynamic bandwidth allocation in OFDM-PON

Orthogonal frequency division multiplexing passive optical network (OFDM-PON) has been considered a promising access solution to meet the variable bandwidth demand. In this paper, a novel scheduling for dynamic bandwidth allocation (DBA) at medium access control (MAC) layer is proposed for uplink transmission of OFDM-PON. In order to utilize the bandwidth efficiently, scheduling in four dimensions is adopted in the proposed DBA algorithm. Four dimensions stand for frequency domains, time domains, modulation formats and power allocations. The algorithm is quite flexible. Simulation results and analysis show that the proposed algorithm can efficiently utilize the OFDM bandwidth and make the system highly energy-efficient.     

Acoustically active perfluorocarbon nanoemulsions as drug delivery carriers for camptothecin: drug release and cytotoxicity against cancer cells

Camptothecin is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. However, its clinical application is limited by its insolubility, instability, and toxicity. The aim of the present study was to develop acoustically active nanoemulsions for camptothecin encapsulation to circumvent these delivery problems. The nanoemulsions were prepared using liquid perfluorocarbons and coconut oil as the cores of the inner phase. These nanoemulsions were stabilized by phospholipids and/or Pluronic F68 (PF68). The nanoemulsions were prepared at high drug loading of ∼100% with a mean droplet diameter of 220-420 nm. Camptothecin in these systems showed retarded drug release. Camptothecin in nanoemulsions with a lower oil concentration exhibited cytotoxicity against melanomas and ovarian cancer cells. Confocal laser scanning microscopy confirmed nanoemulsion uptake into cells. Hemolysis caused by the interaction between erythrocytes and the nanoemulsions was investigated. Formulations with phosphatidylethanolamine as the emulsifier showed less hemolysis than those with phosphatidylcholine. Using a 1 MHz ultrasound, an increased release of camptothecin from the system with lower oil concentration could be established, illustrating a drug-targeting effect.     

Optimal control design of constant amplitude phase-modulated pulses: application to calibration-free broadband excitation

An optimal control algorithm for generating purely phase-modulated pulses is derived. The methodology is applied to obtain broadband excitation with unprecedented tolerance to RF inhomogeneity. Design criteria were transformation of Iz-->Ix over resonance offsets of +/-25 kHz for constant RF amplitude anywhere in the range 10-20 kHz, with a pulse length of 1 ms. Simulations transform Iz to greater than 0.99 Ix over the targetted ranges of resonance offset and RF variability. Phase deviations in the final magnetization are less than 2-3 degrees over almost the entire range, with sporadic deviations of 6-9 degrees at a few offsets for the lowest RF (10 kHz) in the optimized range. Experimental performance of the new pulse is in excellent agreement with the simulations, and the robustness of the excitation pulse and a derived refocusing pulse are demonstrated by insertion into conventional HSQC and HMBC-type experiments.     

Optimal control in NMR spectroscopy: Numerical implementation in SIMPSON

We present the implementation of optimal control into the open source simulation package SIMPSON for development and optimization of nuclear magnetic resonance experiments for a wide range of applications, including liquid- and solid-state NMR, magnetic resonance imaging, quantum computation, and combinations between NMR and other spectroscopies. Optimal control enables efficient optimization of NMR experiments in terms of amplitudes, phases, offsets etc. for hundreds-to-thousands of pulses to fully exploit the experimentally available high degree of freedom in pulse sequences to combat variations/limitations in experimental or spin system parameters or design experiments with specific properties typically not covered as easily by standard design procedures. This facilitates straightforward optimization of experiments under consideration of rf and static field inhomogeneities, limitations in available or desired rf field strengths (e.g., for reduction of sample heating), spread in resonance offsets or coupling parameters, variations in spin systems etc. to meet the actual experimental conditions as close as possible. The paper provides a brief account on the relevant theory and in particular the computational interface relevant for optimization of state-to-state transfer (on the density operator level) and the effective Hamiltonian on the level of propagators along with several representative examples within liquid- and solid-state NMR spectroscopy.     

Targeted and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities

This study investigated the targeting and ultrasound-triggered injury of cancer cells using anticancer drug-free liposomes that contained an emulsion of perfluoropentane (ePFC5) and were co-modified with avidin as a targeting ligand for cancer cells and the hemagglutinating virus of Japan (HVJ) envelope to promote liposome fusion with the cells. These liposomes are designated as ePFC5-loaded avidin/HVJ liposomes. ePFC5-loaded liposomes were sensitized to ultrasound irradiation. Liposomes modified with avidin alone (avidin liposomes) showed binding to MCF-7 human breast cancer cells, and liposomes modified with HVJ envelope alone (HVJ liposomes) were found to fuse with MCF-7 cells. The irradiation of MCF-7 cells with 1 MHz ultrasound (30 s, 1.2 W/cm², duty ratio 30%) combined with ePFC5-loaded avidin/HVJ liposomes resulted in a decrease in cell viability at 1 h after irradiation to 43% of that of controls without ultrasound irradiation or liposomes. The cell viability was lower than that of cells treated with ultrasound irradiation with ePFC5-loaded avidin liposomes or ePFC5-loaded HVJ liposomes. This indicates that co-modification of liposome with avidin and HVJ envelope could enhance ultrasound-induced cell injury in the presence of ePFC5-loaded liposomes.     

Optimal guidance law design for impact with terminal angle of attack constraint

According to the requirements of the precision guidance of air-to-surface weapons with multiple constraints, a new optimal guidance law applying to attack the ground stationary target is designed. On the basis of dividing the 3D movement of the weapon into the movements of diving plane and turning plane, the relative motion of weapon-target is established first. Considering the conditions of miss distance, impact angle and terminal angle of attack, the general formulation of a new guidance law with an arbitrary system order is deduced by solving the Riccati equation of the quadratic optimal control. The approximate expressions of lag free system and first-order lag system are given. The validity of the optimal guidance law is verified by the comparable simulations of the characteristic trajectory. The simulation results shows that the optimal guidance laws satisfy the precision guidance with impact angle constraint as well as the angle of attack converges to zero at final time, which is important for warhead effect.     

Effect of ultrasound irradiation on bacterial internalization and bacteria-mediated gene transfer to cancer cells

The present study demonstrates that ultrasound irradiation can facilitate bacteria-mediated gene delivery (bactofection). Escherichia coli modified with avidin were employed as a vehicle for delivery of the green fluorescent protein (GFP) gene, a model heterologous gene, into the breast cancer cell line MCF-7. Avidin-mediated binding of E. coli to MCF-7 cells enhanced the internalization of E. coli by approximately 17%, irrespective of the use of ultrasound irradiation. Furthermore, the use of ultrasound irradiation increased the internalization by approximately 5%, irrespective of the presence of avidin on the E. coli cell surface. The percentages of GFP-expressing MCF-7 cells at 24 h after bactofection were below 0.5% and 2% for the case with only avidin-modification of E. coli cell surface and only ultrasound irradiation, respectively. However, combining avidin modification with the ultrasound treatment increased this value to 8%. Thus, the use of avidin-modified bacteria in conjunction with ultrasound irradiation has potential as an effective strategy for tumor-targeted bactofection.     

A segmentation based channel scheduling scheme for improving channel utilization in OBS networks

Channel scheduling is an important aspect in optical burst switching (OBS) networks. OBS is a promising solution for the future Internet backbone. In OBS network a key issue is data channel scheduling. In this paper we propose a channel scheduling scheme to optimize channel utilization for OBS networks with segmentation. In this paper, we propose an efficient way to organize the void intervals. The channel scheduling method is compared with existing scheduling schemes. Simulation results show that both channel utilization and burst loss ratio performance improved as compared to existing scheduling schemes.     

A Priori Error Estimates of Finite Element Methods for Linear Parabolic Integro-Differential Optimal Control Problems

In this paper, we study the mathematical formulation for an optimal control problem governed by a linear parabolic integro-differential equation and present the optimality conditions. We then set up its weak formulation and the finite element approximation scheme. Based on these we derive the a priori error estimates for its finite element approximation both in $H^1$ and $L^2$ norms. Furthermore, some numerical tests are presented to verify the theoretical results.     

Optimal real-time estimation in diffusion tensor imaging

Diffusion tensor imaging (DTI) constitutes the most used paradigm among the diffusion-weighted magnetic resonance imaging (DW-MRI) techniques due to its simplicity and application potential. Recently, real-time estimation in DW-MRI has deserved special attention, with several proposals aiming at the estimation of meaningful diffusion parameters during the repetition time of the acquisition sequence. Specifically focusing on DTI, the underlying model of the noise present in the acquired data is not taken into account, leading to a suboptimal estimation of the diffusion tensor. In this paper, we propose an optimal real-time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images.     

Optimal control based NCO and NCA experiments for spectral assignment in biological solid-state NMR spectroscopy

We present novel pulse sequences for magic-angle-spinning solid-state NMR structural studies of (13)C,(15)N-isotope labeled proteins. The pulse sequences have been designed numerically using optimal control procedures and demonstrate superior performance relative to previous methods with respect to sensitivity, robustness to instrumental errors, and band-selective excitation profiles for typical biological solid-state NMR applications. Our study addresses specifically (15)N to (13)C coherence transfers being important elements in spectral assignment protocols for solid-state NMR structural characterization of uniformly (13)C,(15)N-labeled proteins. The pulse sequences are analyzed in detail and their robustness towards spin system and external experimental parameters are illustrated numerically for typical (15)N-(13)C spin systems under high-field solid-state NMR conditions. Experimentally the methods are demonstrated by 1D (15)N-->(13)C coherence transfer experiments, as well as 2D and 3D (15)N,(13)C and (15)N,(13)C,(13)C chemical shift correlation experiments on uniformly (13)C,(15)N-labeled ubiquitin.