Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

共轭梯度法在三维复杂流动数值分析中的应用

将多块网格技术运用于三维T型管复杂流场的网格生成，利用不完全乔列斯基预处理共轭梯度，双共轭梯度方法求解N－S方程的离散方程。计算表明上述方法有良好的收敛特性，适合于诸如T型管等复杂流动的分析。     

宽线性共轭梯度算法及其在盲多用户检测中的应用

本文提出了一种宽线性共轭梯度算法，分析了算法在均值意义下的收敛性，并给出了算法稳定条件。仿真表明，新算法应用于码分多址系统多址干扰抑制时的性能优于Yin（2003）及Schober（2004）所提出的算法。     

Linear Algebra Considerations for the Multi-Threaded Simulation of Mechanical Systems

A solution method suitable for the multi-threaded simulation ofmechanical systems represented in Cartesian coordinates isproposed and analyzed. In a state-space framework for thesolution of the Differential Algebraic Equations (DAE) ofMultibody Dynamics, the position/velocity stabilization and theacceleration computation are based on iterative solvers applied toequivalent reduced problems. The most in-depth computationalaspect analyzed is the preconditioning, i.e., the direct solutionof the reduced systems. Provided a topology index reduction is first applied to the model, the effort for the direct solution of the reduced systems is shown to be of order O(N _J ), where N _J is the number of joints in the model. The recurring theme of thepaper is the central role that the topology of the mechanicalsystem plays in the overall performance of the numericalsimulation. Based on the topology of the model, parallelcomputational threads can be established to start in the equationformulation and continue through the iterative numericalalgorithms employed for the numerical solution. Task schedulingthese parallel threads is expected to redeem real-time performancefor certain classes of complex applications.     

制备方法对复合触头材料导电特性的影响

根据复合材料制备方法的各自特点 ,建立了计算复合触头材料电导率的三维单元网络模型。应用该模型研究了制备方法对材料电导率的影响 ,并与测量值进行了比较。结果表明了这种模型的可行性。     

Solving regularized least squares with qualitatively controlled adaptive cross‐approximated matrices

The adaptive cross‐approximation (ACA) technique is applied to accelerating an inverse‐problem solver that estimates charge distribution on a dielectric spacer. The ACA generates an approximated system‐matrix that enables us to carry out high‐speed inverse calculation. We designed an approximation procedure based on ACA with some additional concepts, that is, (a) partitioning of matrix based on algebraic information, (b) approximation quality control based on matrix norms, and so on. The tested solver (LSQR for regularized least squares) with ACA demonstrates about 10 times faster performance than that without ACA. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(3): 10–18, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20326     

二阶曲线渐近线的等价定义及其应用

给出了射影几何中关于二阶曲线渐近线的几个等价定义,并探讨了根据不同 定义的二阶曲线渐近线的应用．     

Fast parallel Preconditioned Conjugate Gradient algorithms for robot manipulator dynamics simulation

In this paper fast parallel Preconditioned Conjugate Gradient (PCG) algorithms for robot manipulator forward dynamics, or dynamic simulation, problem are presented. By exploiting the inherent structure of the forward dynamics problem, suitable preconditioners are devised to accelerate the iterations. Also, based on the choice of preconditioners, a modified dynamic formulation is used to speedup both serial and parallel computation of each iteration. The implementation of the parallel algorithms on two interconnected processor arrays is discussed and their computation and communication complexities are analyzed. The simulation results for a Puma Arm are presented to illustrate the effectiveness of the proposed preconditioners. With a faster convergence due to preconditioning and a faster computation of iterations due to parallelization, the developed parallel PCG algorithms represent the fastest alternative for parallel computation of the problem withO(n) processors.     

双相位共轭镜的工作条件参数分析

本文讨论了纯扩散机制的光折变晶体用作单作用区的双相位共轭镜（ＤＰＣＭ）时的阈值耦合强度和允许的输入光强比范围，并与双作用区的情况进行比较后，给出了在输入光强比远离１的条件下，双相位共轭镜的正常工作的条件参数。     

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.