Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

关于紧连续L-domain的一个刻画定理

本文从函数空间的Isbell拓扑以及ω-连续性两方面给出了紧连续L-domain的刻画定理。其主要结果是:连续L-domain是Lawson紧的当且仅当函数空间[L→L]的Scott拓扑与Isbell拓扑一致。

Extension of Proper _-holom orphic Mappings

In this paper,we prove that a proper μ holomorphic mapping f:D 1→D 2 between bounded domains with some convexity,such that f satisfies some growth condition,extends smoothly to bD 1-{z:U(z)=0}.

Non-stationary Buffeting Response Analysis of Long Span Suspension Bridge Under Strong Wind Loading

The non-stationary buffeting response of long span suspension bridge in time domain under strong wind loading is computed. Modeling method for generating non-stationary fluctuating winds with probabilistic model for non-stationary strong wind fields is first presented. Non-stationary wind forces induced by strong winds on bridge deck and tower are then given a brief introduction. Finally,Non-stationary buffeting response of Pulite Bridge in China,a long span suspension bridge,is computed by using ANSYS software under four working conditions with different combination of time-varying mean wind and time-varying variance. The case study further confirms that it is necessity of considering non-stationary buffeting response for long span suspension bridge under strong wind loading,rather than only stationary buffeting response.

拟信息基,ω-代数Cpo,和SFP domain

G.Sam b in引入了(代数)信息基的概念,并证明了代数Scott D om a in范畴和信息基范畴是等价的.B.R.C.Bedrega l给出了ω-代数cpo和SFP dom a in的刻划.而G.Q.Zhang通过序结构给出了SFP dom a in的刻划.本文将引入了拟信息基的概念并给出了ω-代数cpo和SFP dom a in的刻划.

北京奥运会徽“中国印”的认知解读

以"中国印,舞动的北京"作为主题的北京奥运会徽蕴含着浓重的中国韵味。它将中国特色、北京特点和奥林匹克运动元素巧妙地结合起来。文章试用认知语言学中的五个基本理论:原型(prototype)、图形-背景(figure-ground)、隐喻(metaphor)、象似性(iconicity)、语域(domain),对"中国印"进行全新视角分析,希望能够达到两个目的:一是帮助学生理解并熟悉掌握这些抽象的认知语言学概念;另一方面又可以加深读者对"中国印"蕴含的丰富含义的正确认知与理解。

家禽天然免疫受体MDA5的作用和相关调控机制

黑色素瘤分化相关基因5（Melanoma differentiation associated gene-5，MDA5）最早在人黑色素瘤细胞中被发现，因其表达受到β-干扰素（IFN-β）转录的调控，又名IFIH1（Interferon induced with helicase C domain 1），也称HELI-CARD和RH116。

Safety evaluation for railway vehicles using an improved indirect measurement method of wheel–rail forces

The wheel-rail force measurement is of great importance to the condition monitoring and safety evaluation of railway vehicles. In this paper, an improved indirect method for wheel-rail force measurement is proposed to evaluate the running safety of railway vehicles. In this method, the equilibrium equations of a suspended wheelset are derived and the wheel-rail forces are then be obtained from measured suspension and inertia forces. This indirect method avoids structural modifications to the wheelset and is applicable to the long-term operation of railway vehicles. As the wheel-rail lateral forces at two sides of the wheelset are difficult to separate, a new derailment criterion by combined use of wheelset derailment coefficient and wheel unloading ratio is proposed. To illustrate its effectiveness, the indirect method is applied to safety evaluation of rail- way vehicles in different scenarios, such as the cross wind safety of a high-speed train and the safety of a metro vehicle with hunting motions. Then, the feasibility of using this method to identify wheel-rail forces for low-floor light rail vehicles with resilient wheels is discussed. The values identified by this method is compared with that by Simpack simulation for the same low-floor vehicle, which shows a good coincidence between them in the time domain of the wheelset lateral force and the wheel-rail vertical force. In addition, use of the method to determine the high-frequency wheel-rail interaction forces reveals that it is possible to identify the high-frequency wheel-rail forces through the accelerations on the axle box.

[D→D](μ)的极大性研究

给出了 [D→D](μ)极大的等价刻划 ,从而解答了KeyeMartin 2 0 0 0年提出的关于具有单调测度的 μ σ连续映射的问题 ,同时还研究了ω

THE SPACES OF CESRO ALMOST CONVERGENT SEQUENCES AND CORE THEOREMS

As known, the method to obtain a sequence space by using convergence field of an infinite matrix is an old method in the theory of sequence spaces. However, the study of convergence field of an infinite matrix in the space of almost convergent sequences is so new （see [15]）. The purpose of this paper is to introduce the new spaces ^ ～f and fo consisting of all sequences whose Ceshro transforms of order one are in the spaces f and ^ ～ f0, respectively. Also, in this paper, we show that ^ ～f and ^ ～f0 are linearly isomorphic to the spaces f and f0, respectively. The β- and γ-duals of the spaces ^ ～f and 2% are computed. Furthermore, the classes （^ ～f： μ） and （μ ： f） of infinite matrices are characterized for any given sequence space μ, and determined the necessary and sufficient conditions on a matrix A to satisfy Bc-core（Ax） K-core（x）, K-core（Ax） Bg-core（x）, Bc-core（Ax） Be-core（x）, Bc-core（Ax） t-core（x） for all x ∈ t∞.

ALMOST CONVERGENCE AND DOUBLE SEQUENTIAL BAND MATRIX

The class f of almost convergent sequences was introduced by G.G. Lorentz, using the idea of the Banach limits [A contribution to the theory of divergent sequences, Acta Math. 80（1948）, 167-190]. Let fo（B） and f（B） be the domain of the double sequential band matrix B（r, s） in the sequence spaces f0 and f. In this article, the β- and γ-duals of the space f（B） are determined. Additionally, we give some inclusion theorems concerning with the spaces f0（B） and f（β）. Moreover, the classes （f（B） ： μ） and （μ： f（B）） of infinite matrices are characterized, and the characterizations of some other classes are also given as an application of those main results, where μ is an arbitrary sequence space.

Enhanced piezoelectricity in 0.7BiFeO_(3)-0.3BaTiO_(3)lead-free ceramics:Distinct effect of poling engineering

BiFeO_(3)-BaTiO_(3) based ceramics are considered to be the most promising lead-free piezoelectric ceramics due to their large piezoelectric response and high Curie temperature.Since the piezoelectric response of piezoelectric ceramics just appears after poling engineering,in this work,the domain evolution and microscopic piezoresponse were observed in-situ using piezoresponse force microscopy(PFM)and switching spectroscopy piezoresponse force microscopy(SS-PFM),which can effectively study the local switching characteristics of ferroelectric materials especially at the nanoscale.The new domain nucleation preferentially forms at the boundary of the relative polarization region and expands laterally with the increase of bias voltage and temperature.The maximum piezoresponse(Rs),remnant piezoresponse(Rrem),maximum displacement(Dmax)and negative displacement(Dneg)at 45 V and 120C reach 122,69,127 pm and 75 pm,respectively.Due to the distinct effect of poling engineering in full domain switching,the corresponding d33 at 50 kV/cm and 120C reaches a maximum of 205 pC/N,which is nearly twice as high as that at room temperature.Studying the evolution of ferroelectric domains in the poling engineering of BiFeO_(3)-BaTiO_(3)ceramics provides an insight into the relationship between domain structure and piezoelectric response,which has implications for other piezoelectric ceramics as well.

有界完备的domain范畴是monadic范畴

一个连续格就是一个完备的连续偏序集,一个有界完备domain则是一个有定向并与非空交的连续偏序集.1975年,Day证明了连续格范畴是集合范畴和T_0拓扑空间范畴上的monadic范畴.本文作者把这一结论推广到了有界完备domain范畴:对任意无限基数κ,作者引入了有界完备的κ-domain以及相应的Scottκ拓扑的概念。并证明了有界完备的κ-domain范畴是集合范畴和T_0的κ拓扑空间范畴上的monadic范畴.

FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis

Angiogenic factor with G-patch and FHA domains 1(AGGF1) exhibits a dynamic distribution from the nucleus to the cytoplasm in endothelial cells during angiogenesis, but the biological significance and underlying mechanism of this nucleocytoplasmic transport remains unknown. Here, we demonstrate that the dynamic distribution is essential for AGGF1 to execute its angiogenic function. To search the structural bases for this nucleocytoplasmic transport, we characterized three potential nuclear localization regions, one potential nuclear export region, forkhead-associated(FHA), and G-patch domains to determine their effects on nucleocytoplasmic transport and angiogenesis, and we show that AGGF1 remains intact during the dynamic subcellular distribution and the region from 260 to 288 amino acids acts as a signal for its nuclear localization. The distribution of AGGF1 in cytoplasm needs both FHA domain and 14-3-3α/β. Binding of AGGF1 via FHA domain to 14-3-3α/β is required to complete the transport. Thus, we for the first time established structural bases for the nucleocytoplasmic transport of AGGF1 and revealed that the FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis.

TGF-β1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression

Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.