Integrated Organ-on-a-chip with Human-induced Pluripotent Stem Cells Directional Differentiation for 3D Skin Model Generation

Keratinocytes and fibroblasts,derived from hiPSCs,were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid)(PLGA)nanofibers and a human skin-on-a-chip device.Unlike the conventional culture dish method,two different epidermal cells are successfully adhered to the front and back sides of the patch,which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin.As expected,the differentiated hiPSCs show the expression of keratinocyte-and fibroblast-specific proteins on the patch,and the layering is found between these two kinds of cells,indicating that this approach creates a powerful in vitro system for modeling skin development and diseases.

Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells

Overexpression of receptor-interacting protein 140（RIP140） promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2（ERK1/2） signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

Silk Fibroin Scaffolds Direct Neural and Glial Differentiation from Embryonic Stem Cells

Spinal cord injury repair is one of the major challenges in medicine,as it can lead to permanent loss of function of central nervous system and damage to other function of the body.Stem cell transplantation together with tissue engineering is increasingly becoming a potential choice of treatment.However,direct transplantation of stem cells without scaffolds has yielded poor clinical outcome.Here we show a strategy of using mouse embryonic stem cells(ESCs)cultured within a silk fibroin(SF)based,three-dimensional scaffold with oriented channels by a directional temperature field freezing technique and lysophilization.We find that the ESCs maintained proliferation and migrated in the scaffolds and the cells migrated fastest along the SF channels.SF scaffolds contributed to ESC differentiation into neural and glial cell like cells and expressions of the neural and glial cell markers MAP2 and GFAP were greatly elevated when retinoic acid was used as an inducing factor.Our results suggest that this approach may offer some hope in the future for spinal cord injury repair using SF scaffolds and ESCs.

Activin-Directed Differentiation of Human Embryonic Stem Cells Differentially Modulates Alveolar Epithelial Wound Repair via Paracrine Mechanism

Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.

Neurotoxic role of interleukin-17 in neural stem cell differentiation after intracerebral hemorrhage

Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.

LIMITING DIRECTION AND BAKER WANDERING DOMAIN OF ENTIRE SOLUTIONS OF DIFFERENTIAL EQUATIONS

In this paper, we mainly investigate entire solutions of complex differential equations with coefficients involving exponential functions, and obtain the dynamical properties of the solutions, their derivatives and primitives. With some conditions on coefficients, for the solutions, their derivatives and their primitives, we consider the common limiting directions of Julia set and the existence of Baker wandering domain.

Differential evolution with controlled search direction

A novel and simple technique to control the search direction of the differential mutation was proposed.In order to verify the performance of this method,ten widely used benchmark functions were chosen and the results were compared with the original differential evolution(DE)algorithm.Experimental results indicate that the search direction controlled DE algorithm obtains better results than the original DE algorithm in term of the solution quality and convergence rate.

LIMITING DIRECTIONS OF JULIA SETS OF ENTIRE SOLUTIONS TO COMPLEX DIFFERENTIAL EQUATIONS

In this paper,we mainly investigate the dynamical properties of entire solutions of complex differential equations.With some conditions on coefficients,we prove that the set of common limiting directions of Julia sets of solutions,their derivatives and their primitives must have a definite range of measure.

JULIA LIMITING DIRECTIONS OF ENTIRE SOLUTIONS OF COMPLEX DIFFERENTIAL EQUATIONS

For entire or meromorphic function f,a value θ∈[0,2π)is called a Julia limiting direction if there is an unbounded sequence{z_(n)}in the Julia set satisfying limn→∞ arg z_(n)=θ.Our main result is on the entire solution f of P(z,f)+F(z)f^(s)=0,where P(z,f)is a differential polynomial of f with entire coefficients of growth smaller than that of the entire transcendental F,with the integer s being no more than the minimum degree of all differential monomials in P(z,f). We observe that Julia limiting directions of f partly come from the directions in which F grows quickly.

Differential interformational velocity analysis as an effective direct hydrocarbon indicator under velocity reversal conditions,an example from the anomalously high temperature and over-pressured DF1-1 Gas Field in the Yinggehai Basin,South China Sea

In the DF1-1 Gas Field in the Yinggehai Basin, South China Sea, the velocity-depth plot and velocity spectra show significant variations from a linear trend, exhibiting a distinct reversal phenomenon. Velocity parameters derived from velocity spectral analysis of the seismic data and sonic logs indicate that the interval velocity reverses below 2,100 m (2.2 s two-way time (TWT)) in the DF1-1 Gas Field. Some direct hydrocarbon indicators (DHIs) models developed for the shallow strata cannot be simply applied to the moderately to deeply buried strata for direct exploration target recognition because the velocity reversal has caused the middle-deep gas reservoirs to exhibit a moderate or weak seismic amplitude. The hydrocarbon indicator method of “Differential Interformational Velocity Analysis (DIVA)” with the aid of other hydrocarbon indicating techniques was employed to effectively identify DHIs in the middle-deep strata under velocity inversion. The result has shown that the DIVA technique can be effectively used as a DHI in both the shallow and the middle-deep strata in the study area with the shallow strata characterized by Type I DIVA anomaly and the middle-deep strata characterized by the Type II DIVA anomaly.

On the Product of Integro Differential Equations and Their Solutions in Direct Sum Spaces

In this paper, we consider a general quasi-differential expressions t1,t2 Tn, each of order n with complex coefficients and their formal adjoints are t1＋,t2＋- x＋ on [0, b） respectively. We show in the direct sum spaces LZ（Ip）, p = 1,2 N of functions defined on each of the separate intervals with the case of one singular end-points and under suitable conditions on the function F that all solutions of the product quasi-integro differential equations are bounded and LZw -bounded on [0,b）.

A NOTE ON THE JULIA SETS OF ENTIRE SOLUTIONS TO DELAY DIFFERENTIAL EQUATIONS

Let f be an entire solution of the Tumura-Clunie type non-linear delay differential equation.We mainly investigate the dynamical properties of Julia sets of f,and the lower bound estimates of the measure of related limiting directions is verified.

Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells

Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to

基于压差法的波向测量方法初步研究

为解决波向测量误差大的问题,本文首次提出了一种基于压差法的波向测量新技术,根据海浪的运动变化规律,在这里巧妙地引进了压差技术,通过对放置在水下一个圆环上多个压力传感器同圆心点上的压差变化进行分析可以得出,圆环上不同方向上的压力传感器同圆心点上的压力传感器之间的差值及相位是随波浪方向变化而变化的,对圆环上不同方向上的压力传感器同圆心点上的压力传感器之间的差值进行分析,找出变化规律与波向的关系,以此得出真实的波向分布。本文通过波浪水池实验验证了该方法的可行性,并通过对实验数据的解析初步得出了压差变化规律与波向的变换关系。

不平行方向导数下的二元函数全微分

通过利用线性代数中自变量空间的基变换方法,推演出二元函数全微分的两个方向不平行的方向导数的线性组合表示,然后在自变量空间的一般可逆变换下推演出全微分的这种表示,推广了二元函数全微分的表示形式,并解释了其几何意义.

中英高等教育管理体系构建方向的差异性对比研究

随着国际、国内环境的不断变化和高等教育管理内部模式的不完善,高等教育管理体系弊病丛生,羁绊高等教育的发展。该文通过中英高等教育管理体系建构方向的差异性对比,拟从中找出值得借鉴的教育管理方法。通过对比分析发现,中国高等教育管理体系在社会教育资源管理、课程设置合理性评价、教育模式的时代适应性方面存在发展优势,同时发现英国高等教育管理体系中的个性化、人性化、开放性发展理念的意义与价值。当今时代,我国高等教育管理需要进一步创新,以适应不断变化的时代发展;体系需要进一步完备,不断满足师生的各种需求。若能将英国高等教育管理体系中的自由、民主、个性化、人本化、开放性和时效性等理念融入其中,将对中国高等教育管理体系的深层次优化产生积极的影响。

飞机多层金属铆接结构缺陷检测的新型电涡流探头仿真设计

飞机多层金属铆接结构随着飞机服役时间的增加,并伴随极端服役环境,有可能出现疲劳裂纹等缺陷,及时发现缺陷并获取缺陷深度、方向等信息对损伤评估与维修具有重要意义。然而,由于多层结构带来的缺陷隐蔽性,导致常规电涡流探头检测信号特征不明显,且常规电涡流探头对某些方向缺陷不敏感,难以判断疲劳裂纹走向。针对上述问题,设计了一种十字跑道型差分式涡流探头,主要由一个十字跑道型激励线圈和两组差分检测线圈组成。通过建立飞机多层金属铆接结构缺陷检测的三维有限元模型研究新型涡流探头的可行性,包括对探头的结构进行了优化,分别对缺陷的不同方向、埋深和提离高度进行了仿真计算。结果表明,新型探头能够有效检测埋深6 mm、尺寸为10 mm×1 mm×1 mm的深层缺陷,并且能够获取缺陷的方向信息。相较传统探头,设计探头具有非敏感方向不漏检、抗提离效应、分辨力高等优势,研究结果可对飞机多层金属铆接结构检测的电涡流探头设计提供一定的参考。

含微分平坦控制的柔直输电系统稳定性分析

交流系统不对称运行时换流站控制参数不合理的取值会影响柔性直流输电系统稳定运行。为此,首先提出不对称工况下含微分平坦控制的换流站小信号模型,同时结合模块化多电平换流器(modular multilevel converter,MMC)内部特性、环流抑制器以及直流线路等各子部分的动态模型,建立两端柔性直流输电系统全局小信号模型;然后在此基础上,依据微分平坦控制器内、外环控制参数根轨迹的变化情况,分析其对系统稳定性的影响,确定其合理取值范围;最后在PSCAD/EMTDC中搭建含微分平坦控制的两端柔性直流输电测试系统,验证所提小信号模型以及结论的正确性,为实际工程中控制器参数整定提供理论依据。

线性微分方程无穷下级整函数解的Baker游荡域

利用Nevanlinna理论和复方程中的比较定理研究了线性微分方程。当方程系数和非齐次项具有公共的非超越方向时,无穷下级的整函数解及其任意阶导数、原函数均没有Baker游荡域。此外,当方程系数有公共的非超越方向且非齐次项的级有穷时,结论依然成立。

基于微分约束的改进自适应多波束抗干扰算法

卫星导航抗干扰技术作为导航接收机中最重要的部分之一,将直接决定导航定位的可靠性和准确性。自适应多波束导航抗干扰技术作为目前抗干扰性能最高的抗干扰技术,其不仅可以对干扰方向进行抑制,还可以对卫星信号方向产生增益,为导航信号提供有效保护。但自适应多波束抗干扰算法需要实时获取卫星信号相对天线阵面的入射角信息,在实际工程应用中,考虑到惯导的姿态测量误差以及载体平台的运动,获取的入射角信息存在一定的偏差,滤波后会引起信号损失。针对这个问题,提出一种基于微分约束的改进自适应多波束抗干扰算法。该方法以LCMV准则为目标函数,通过在卫星信号入射方向和干扰方向上增加一定角度范围进行约束,削弱入射角度偏差引起的信号损失。仿真结果表明,该方法在一定的角度偏差范围内可有效保护卫星信号并抑制干扰信号,从而提高抗干扰性能。