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利用核移植技术生产人类疾病大鼠模型的研究   总被引:16,自引:0,他引:16       下载免费PDF全文
大鼠是研究人类疾病的理想模型动物,而利用核移植手段是创造遗传修饰大鼠的最佳手段。但由于大鼠卵母细胞和胚胎发育的特殊性,克隆大鼠一直没有取得成功。我们在对大鼠卵细胞活化进行了深入研究的基础上,采用了全新的快速一步法体细胞核移植技术,并且利用蛋白激酶抑制剂(MG132)阻断大鼠卵母细胞减数分裂中期到后期的转变,成功地创造出有繁殖能力的体细胞克隆大鼠。该项研究为人类疾病的研究、相关药物的研制创造了条件。  相似文献   

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The general mth order difference equation X(n+m)+a1X(n+m?1)+…+amX(n) = F[n,X(n),…,X(n+m?1)] is considered. The stability properties of its solutions are studied using the discrete form of Liapunov's direct method. A quadratic form is selected as a possible Liapunov function V(n,X) and a scheme is developed for determining appropriate conditions on this function to insure that its total difference ΔV(n,X) is negative semi-definite or negative definite with respect to the difference equation. The approach is applied to the fourth-order difference equation in full detail to illustrate the method for determining the conditions which imply either uniform stability or uniform asymptotic stability and specific results are obtained. Several comments on, and extensions of, the work done by Puri and Drake for the cases m = 2 and m = 3 are presented.The results of the present approach in the homogeneous case where F[n,X(n),…,X(n+m?1)] = 0 are compared with the usual Schur-Cohn criteria and are shown to be at least as good.  相似文献   

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Bio-electrosprays (BESs) provide a means of precisely manipulating cells and thus have the potential for many clinical uses such as the generation of artificial tissues∕organs. Previously we tested the biological safety of this technology with a variety of living cells and also embryos from the vertebrate model organisms Danio rerio (zebrafish) and Xenopus tropicalis (frog). However, the viability and fertility of the treated embryos could not be fully assessed due to animal licensing laws. Here we assay the viability and fertility of Drosophila melanogaster (fruit fly) embryos in conjunction with the bio-electrospray procedure. Bio-electrosprayed Drosophila embryos developed into fully fertile adult flies that were indistinguishable from wild-type. Thus, we demonstrate that the bio-electrospray procedure does not induce genetic or physical damage that significantly affects the development or fertility of a multicellular organism. This study along with our previous investigations demonstrates the potential of this approach to be developed for the precise manipulation of sensitive biological materials.  相似文献   

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In a typical inverted-file full-text document retrieval system, the user submits queries consisting of strings of characters combined by various operators. The strings are looked up in a text-dictionary which lists, for each string, all the places in the database at which it occurs. It is desirable to allow the user to include in his query truncated terms such as X1, 1X, 1X1, or X1Y, where X and X are specified strings and 1 is a variable-length-don't-care character, that is, 1 represents an arbitrary, possibly empty, string. Processing these terms involves finding the set of all words in the dictionary that match these patterns. How to do this efficiently is a long-standing open problem in this domain.In this paper we present a uniform and efficient approach for processing all such query terms. The approach, based on a “permuted dictionary” and a corresponding set of access routines, requires essentially one disk access to obtain from the dictionary all the strings represented by a truncated term, with negligible computing time. It is thus well suited for on-line applications. Implementation is simple, and storage overhead is low: it can be made almost negligible by using some specially adapted compression techniques described in the paper.The basic approach is easily adaptable for slight variants, such as fixed (or bounded) length don't-care characters, or more complex pattern matching templates.  相似文献   

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The set of papers [3], [4], [6] and [7] (Chattopadhyay et al., 1999; Dihidar and Choudhury, 2004; Khan et al., 1997, 1999) deals with the behavior of the uniform two-dimensional cellular automata over binary fields (Z2). Some structural properties and precise mathematical models using matrix algebra over the field Z2 are reported for characterizing the behavior of two-dimensional nearest neighborhood linear cellular automata with null and periodic boundary conditions [3], [4], [6] and [7] (Chattopadhyay et al., 1999; Dihidar and Choudhury, 2004; Khan et al., 1997, 1999). In this paper, we characterize two-dimensional linear cellular automata transformations by using matrix algebra built on Z3. We analyze some results for two-dimensional CA with rule numbers 2460N and 2460P. Finally, we investigate the dimension of the kernel of two-dimensional cellular automata defined by the rule number 2460N.  相似文献   

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In spite of the vast amount of work on subjectivity and sentiment analysis (SSA), it is not yet particularly clear how lexical information can best be modeled in a morphologically-richness language. To bridge this gap, we report successful models targeting lexical input in Arabic, a language of very complex morphology. Namely, we measure the impact of both gold and automatic segmentation on the task and build effective models achieving significantly higher than our baselines. Our models exploiting predicted segments improve subjectivity classification by 6.02% F1-measure and sentiment classification by 4.50% F1-measure against the majority class baseline surface word forms. We also perform in-depth (error) analyses of the behavior of the models and provide detailed explanations of subjectivity and sentiment expression in Arabic against the morphological richness background in which the work is situated.  相似文献   

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Somatic mutations of the chromatin remodeling gene ARID2 are observed in ∼7% of human lung adenocarcinomas (LUADs). However, the role of ARID2 in the pathogenesis of LUADs remains largely unknown. Here we find that ARID2 expression is decreased during the malignant progression of both human and mice LUADs. Using two KrasG12D-based genetically engineered murine models, we demonstrate that ARID2 knockout significantly promotes lung cancer malignant progression and shortens overall survival. Consistently, ARID2 knockdown significantly promotes cell proliferation in human and mice lung cancer cells. Through integrative analyses of ChIP-Seq and RNA-Seq data, we find that Hspa1a is up-regulated by Arid2 loss. Knockdown of Hspa1a specifically inhibits malignant progression of Arid2-deficient but not Arid2-wt lung cancers in both cell lines as well as animal models. Treatment with an HSPA1A inhibitor could significantly inhibit the malignant progression of lung cancer with ARID2 deficiency. Together, our findings establish ARID2 as an important tumor suppressor in LUADs with novel mechanistic insights, and further identify HSPA1A as a potential therapeutic target in ARID2-deficient LUADs.  相似文献   

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Microfluidics approaches have gained popularity in the field of directed cell migration, enabling control of the extracellular environment and integration with live-cell microscopy; however, technical hurdles remain. Among the challenges are the stability and predictability of the environment, which are especially critical for the observation of fibroblasts and other slow-moving cells. Such experiments require several hours and are typically plagued by the introduction of bubbles and other disturbances that naturally arise in standard microfluidics protocols. Here, we report on the development of a passive pumping strategy, driven by the high capillary pressure and evaporative capacity of paper, and its application to study fibroblast chemotaxis. The paper pumps—flowvers (flow + clover)—are inexpensive, compact, and scalable, and they allow nearly bubble-free operation, with a predictable volumetric flow rate on the order of μl/min, for several hours. To demonstrate the utility of this approach, we combined the flowver pumping strategy with a Y-junction microfluidic device to generate a chemoattractant gradient landscape that is both stable (6+ h) and predictable (by finite-element modeling calculations). Integrated with fluorescence microscopy, we were able to recapitulate previous, live-cell imaging studies of fibroblast chemotaxis to platelet derived growth factor (PDGF), with an order-of-magnitude gain in throughput. The increased throughput of single-cell analysis allowed us to more precisely define PDGF gradient conditions conducive for chemotaxis; we were also able to interpret how the orientation of signaling through the phosphoinositide 3-kinase pathway affects the cells’ sensing of and response to conducive gradients.  相似文献   

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《Research Policy》2019,48(7):1758-1770
In recent years, several organizations have opened up their innovation processes to individuals from outside of the organization by means of digital crowdsourcing. The literature on crowdsourcing has emphasized the importance of using digital technology to reach far beyond organizational boundaries and include individuals with (educational) backgrounds that are very different and unrelated to those within the organization in its innovation process. It has been argued that such individuals will contribute novel insights because they consider an organization's innovation challenge from different perspectives. Building on the literature on creativity and absorptive capacity, we instead argue that having a related perspective will positively affect an individual's idea performance, while unrelated perspectives only positively contribute to idea performance in combination with a related perspective. Analyses of 2178 ideas contributed by 948 crowd members to 68 crowdsourced idea challenges show that it is important to consider how (educational) backgrounds can provide individuals with multiple perspectives, which can be either related or unrelated, and study how the interplay of related and unrelated perspectives affects the value of ideas in organizational open innovation initiatives.  相似文献   

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Population admixture results in genome-wide combinations of genetic variants derived from different ancestral populations of distinct ancestry, thus providing a unique opportunity for understanding the genetic determinants of phenotypic variation in humans. Here, we used whole-genome sequencing of 92 individuals with high coverage (30–60×) to systematically investigate genomic diversity in the Uyghurs living in Xinjiang, China (XJU), an admixed population of both European-like and East-Asian-like ancestry. The XJU population shows greater genetic diversity, especially a higher proportion of rare variants, compared with their ancestral source populations, corresponding to greater phenotypic diversity of XJU. Admixture-induced functional variants in EDAR were associated with the diversity of facial morphology in XJU. Interestingly, the interaction of functional variants between SLC24A5 and OCA2 likely influences the diversity of skin pigmentation. Notably, selection has seemingly been relaxed or canceled in several genes with significantly biased ancestry, such as HERC2OCA2. Moreover, signatures of post-admixture adaptation in XJU were identified, including genes related to metabolism (e.g. CYP2D6), digestion (e.g. COL11A1), olfactory perception (e.g. ANO2) and immunity (e.g. HLA). Our results demonstrated population admixture as a driving force, locally or globally, in shaping human genetic and phenotypic diversity as well as in adaptive evolution.  相似文献   

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In this paper we study boundary value problems for anisotropic partial differential-operator equations with parameters. The principal part of the appropriate differential operators are not self-adjoint. Several conditions for the uniform separability in weighted Banach-valued Lp-spaces are given. Sharp estimates for the resolvent of the corresponding differential operator are obtained. In particular the positivity and R-positivity of these operators are established. As an application we study the separability of degenerate DOEs, maximal regularity for degenerate abstract parabolic problem with parameters, the uniform separability of finite and infinite systems for degenerate anisotropic partial differential equations with parameters.  相似文献   

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The traditional approach to fault-tolerant computation has been via modular hardware redundancy. Although universal and simple, modular redundancy is inherently expensive and inefficient. By exploiting particular structural features of a computational architecture or an algorithm, arithmetic codes and recently developed algorithm-based fault tolerance (ABFT) techniques manage to introduce “analytical redundancy” and offer more efficient fault coverage at the cost of narrower applicability and harder design. In this paper, we extend a variety of results and constructive procedures that were developed in previous work for computations that take place in an abelian group to a more general setting that considers computations in semigroups. We demonstrate possible encodings for semigroup operations of interest and use our extension to design concurrent error detection and correction schemes for group and semigroup machines. The method provides insight regarding the role of decomposition in fault-tolerant algebraic machines and results in a general, hardware-independent characterization of concurrent error detection and correction in finite semiautomata. We also demonstrate that by extending this approach to other dynamic systems, with specific hardware implementations and failure modes, we can systematically obtain fault-tolerant architectures. More specifically, we apply these techniques to linear time-invariant dynamic systems and Petri net models of discrete event systems.  相似文献   

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To cope with ambiguous and/or underspecified queries, search result diversification (SRD) is a key technique that has attracted a lot of attention. This paper focuses on implicit SRD, where the subtopics underlying a query are unknown. Many existing methods appeal to the greedy strategy for generating diversified results. A common practice is using a heuristic criterion for making the locally optimal choice at each round. As a result, it is difficult to know whether the failures are caused by the optimization criterion or the setting of parameters. Different from previous studies, we formulate implicit SRD as a process of selecting and ranking k exemplar documents through integer linear programming (ILP). The key idea is that: for a specific query, we expect to maximize the overall relevance of the k exemplar documents. Meanwhile, we wish to maximize the representativeness of the selected exemplar documents with respect to the non-selected documents. Intuitively, if the selected exemplar documents concisely represent the entire set of documents, the novelty and diversity will naturally arise. Moreover, we propose two approaches ILP4ID (Integer Linear Programming for Implicit SRD) and AP4ID (Affinity Propagation for Implicit SRD) for solving the proposed formulation of implicit SRD. In particular, ILP4ID appeals to the strategy of bound-and-branch and is able to obtain the optimal solution. AP4ID being an approximate method transforms the target problem as a maximum-a-posteriori inference problem, and the message passing algorithm is adopted to find the solution. Furthermore, we investigate the differences and connections between the proposed models and prior models by casting them as different variants of the cluster-based paradigm for implicit SRD. To validate the effectiveness and efficiency of the proposed approaches, we conduct a series of experiments on four benchmark TREC diversity collections. The experimental results demonstrate that: (1) The proposed methods, especially ILP4ID, can achieve substantially improved performance over the state-of-the-art unsupervised methods for implicit SRD. (2) The initial runs, the number of input documents, query types, the ways of computing document similarity, the pre-defined cluster number and the optimization algorithm significantly affect the performance of diversification models. Careful examinations of these factors are highly recommended in the development of implicit SRD methods. Based on the in-depth study of different types of methods for implicit SRD, we provide additional insight into the cluster-based paradigm for implicit SRD. In particular, how the methods relying on greedy strategies impact the performance of implicit SRD, and how a particular diversification model should be fine-tuned.  相似文献   

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In recent works several authors have considered the L1 fidelity term, the L2 fidelity term and the combined L1 and L2 fidelity term for denoising models, and they used the fast Fourier transform (FFT) algorithm which can only use periodic boundary conditions (BCs). In this paper, we combine the augmented Lagrangian method (ALM) and the symmetric Red–Black Gauss–Seidel (SRBGS) method to propose three algorithms that are suitable for different BCs. Experimental results show that the proposed algorithms are effective and the model with the combined L1 and L2 fidelity term demonstrates more advantages in efficiency and accuracy than other models with the L1 fidelity term or the L2 fidelity term.  相似文献   

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猪体细胞核移植研究进展   总被引:1,自引:0,他引:1  
由于猪的器官极可能成为人类未来器官的供应源,猪体细胞核移植及 转基因等方面的研究已成为全球的热点。近几年来,猪体细胞核移植研究取得了一定的进展,但总体看来核移植效率还很低(<1%),还需要不断完善核移植程序及对一些基础问题的 深入研究。本文对猪体细胞核移植研究进展及面临的一些问题作一综述与分析,旨在为研究 者提供一些有益的启示。  相似文献   

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This paper is concerned with the observer-based H finite-time control problem for linear parameter-varying (LPV) systems with parameter-varying time delays and external disturbance. The main contribution is to design an observer-based H finite-time controller such that the resulting closed-loop system is uniformly finite-time bounded and satisfies a prescribed H disturbance attenuation level in a finite-time interval. By using the delay- and parameter-dependent multiple Lyapunov–Krasovskii functional approach, sufficient criteria on uniform H finite-time stabilization via observer-based state feedback are presented for the solvability of the problem, which can be tackled by a feasibility problem in terms of linear matrix inequalities. Finally, numerical examples are given to illustrate the validity of the proposed theoretical results.  相似文献   

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