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The putative window of embryo implantation in the human opens between days 19--24 of the menstrual cycle. During this period, the endometrium undergoes distinctive structural and functional changes orchestrated by steroid hormones, growth factors, and cytokines to attain a receptive phase in which it acquires the ability to implant the developing embryo. A major challenge in the study of human reproduction is to identify the molecular signals that participate in the establishment of this critical receptive phase in the context of the natural cycle. Toward this goal, we analyzed human endometrial biopsies at various days of the menstrual cycle by employing messenger RNA (mRNA) differential display technique. We isolated several complementary DNAs representing genes that are either up- or down-regulated within the putative window of implantation. We identified one of these genes as that encoding interferon (IFN)-inducible guanylate-binding protein 1 (or GBP1), which possesses GTPase activity. Analysis of endometrial biopsies by Northern blotting and RT-PCR demonstrated that GBP1 mRNA is specifically induced at the midsecretory phase of the menstrual cycle. In situ hybridization analysis revealed that GBP1 mRNA expression is localized in the glandular epithelial cells as well as in the stroma in the immediate vicinity of the glands. We observed that treatment of human endometrial adenocarcinoma cell, Ishikawa, with IFN-gamma or IFN-alpha markedly induced the expression of GBP1 mRNA. IFN-gamma was, however, a more potent inducer of GBP1 than IFN-alpha. Consistent with this finding, the temporal profile of GBP1 expression during the menstrual cycle resembled that of IFN-gamma mRNA more closely than that of IFN-alpha, predicting a regulatory role of IFN-gamma in GBP1 expression in midsecretory human endometrium. Although the precise function of GBP1 in the receptive human uterus remains unclear, its unique expression overlapping the putative window of implantation suggests that it might serve as a useful marker of uterine receptivity in the human.

Implantation of the developing blastocyst is regulated by multiple effectors, such as steroid hormones, growth factors, and cytokines. To understand how these diverse signaling pathways interact to modulate uterine gene expression, we employed a gene expression screen technique to identify the molecules that are induced in the periimplantation rat uterus. Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1). This gene exhibits significant homology to interferon (IFN)-alpha/beta-inducible human genes p27 and 6-16, indicating that these genes may belong to the same family. Consistent with this finding, expression of IRG1 messenger RNA (mRNA) in rat uterus increased about 20-fold in response to IFNalpha. Uterine expression of IRG1 was also stimulated by estrogen and was partially inhibited by an antiestrogen, ICI 182,780. In pregnant rats, IRG1 expression was high on day 1, but declined on days 2 and 3. The level of IRG1 mRNA again rose transiently on day 4 immediately preceding implantation. In situ hybridization analysis localized the IRG1 mRNA expression in the endometrial epithelium and the surrounding stroma. Interestingly, the expression of p27, which shows high homology to IRG1, was strongly enhanced in human endometrium during the midsecretory phase of the menstrual cycle, overlapping the putative window of implantation. Both IRG1 and p27 mRNAs are therefore induced in the endometrium in an implantation stage-specific manner. We also observed a synergistic interaction between IFNalpha and estrogen receptor signaling pathways that led to maximal induction of p27 mRNA in Ishikawa cells. Although the functional roles of IRG1 and p27 remain unclear, we describe for the first time, identification of a gene family regulated by IFNalpha in both rodent and human uteri. More importantly, our studies reveal that a complex interplay between the steroid hormone and IFN pathways regulates the expression of these genes in the endometrium at the time of implantation.

The steroid hormone estrogen profoundly influences the early events in the uterus leading to embryo implantation. It is thought that estrogen triggers the expression of a unique set of genes in the preimplantation endometrium that in turn control implantation. To identify these estrogen-induced genes, we used a delayed implantation model system in which embryo attachment to endometrium is dependent on estrogen administration. Using a mRNA differential display (DD) method, we isolated a number of cDNAs representing mRNAs whose expression is either turned on or turned off in response to an implantation-inducing dose of estrogen. We identified one of these cDNAs as that encoding rab11, a p21ras-like GTP-binding protein (G protein), which functions in the targeting of transport vesicles to the plasma membrane. In normal pregnant rats, rab11 mRNA was expressed at low levels on days 1–2 of pregnancy, but its expression was markedly enhanced (∼6- to 8-fold) between days 3–5 immediately before implantation. In situ hybridization and immunocytochemistry revealed that rab11 expression in the uterus was predominantly in the glandular epithelium. In ovariectomized rats, the expression of rab11 mRNA was induced in the endometrium in response to estrogen. To determine whether this effect of estrogen was mediated through its nuclear receptors, we examined rab11 expression in a transformed endometrial cell line, Ishikawa. In transient transfection experiments, we observed that overexpression of estrogen receptor (ER) α or β induced endogenous rab11 mRNA in a hormone-dependent manner. ER bound to an antagonist, ICI 182,780, failed to activate this gene expression. These findings, together with the observation that ERα but not ERβ is detected in the glands of the preimplantation uterus, indicate that rab11 is one of the proteins that are specifically induced by estrogen-complexed ERα in rat endometrium at the onset of implantation. Our results imply that estrogen, which induces the synthesis of many growth factors and their receptors and other secretory proteins that are thought to be critical for implantation, may also facilitate their transport to the membrane and/or secretion by stimulating the expression of rab11, a component of the membrane-trafficking pathway. This study therefore provides novel insights into the diverse cellular mechanisms by which estrogen, acting via its nuclear receptors, may influence blastocyst implantation.

The purpose of this study is to illustrate the challenges and barriers encountered in E-Government development and implementation in Sudan. The study described the E- Government initiatives and pointed out the benefits of E- Government which could be realized throughout the adoption of E-Government. The study suggested some priority areas of E- Government initiatives in Sudan. The study also discussed Sudan E-Government current status. Therefore, it outlined the barriers and challenges impeded Sudan E-Government development. The study stated the country readiness for E-Government adoption weaknesses. Finally, the study recommended that proper orientation should be given to E-Government adoption and development in Sudan.

Aiming at the issue of precise location for the mobile robot underground coal mine, propose three-point calculation of close distance and Gaussian filter, use the classical logarithmic distance attenuation model as a platform, create a node backstepping algorithm model. The main research of the algorithm is as follows: how to determine the reference node which is the closest to the mobile node and the parameters the closest to the mobile node; how the reference node to deal with the RSSI information received from the other reference nodes can obtain the best A, n value used for positioning.

Home service robots need to solve the problem of accurate location when they move. Aiming at the issue of current positioning theory's accuracy is not high, combine the classical logarithmic distance attenuation model, propose a near distance three-point calculating method, create a node back stepping algorithm model, give the best dynamic A and n values to the positioning node when they're positioning. The experimental results show that the accuracy of dynamic value is higher than static value and it's mainly not affected by environment when using dynamic value to locate.

In order to respond to environmental uncertainty, deep understanding, flexibility, and analysis of evolution of supply chain flexibility in changeable demand environment is the primary goal in supply chain management. With the continuous updation of technology and various customers’ requirements, supply chain flexibility has received increasing attention by practitioners as well as researchers. This paper analyzed the concept of supply chain flexibility evolution and division of the flexibility capacity of supply chain. Then it presented the construction stages and evolution factors of the supply chain flexibility. Due to the timeliness and dynamics of supply chain flexibility, supply chain has to dynamically adjust and real-time monitor the degree of flexibility. Finally, this paper established the evolution mechanism and evolution framework of supply chain flexibility, which is essential to construct an effective supply chain and has deep theoretical and practical values.

TB filled in by Laureen Please see later in the article for the Editors' Summary, Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary, Editors' Summary Background Cancer, which is responsible for 13% of global deaths, can develop anywhere in the body, but all cancers are characterized by uncontrolled cell growth and reduced cellular differentiation (the process by which unspecialized cells such as “stem” cells become specialized during development, tissue repair, and normal cell turnover). Genetic alterations—changes in the sequence of nucleotides (DNA's building blocks) in specific genes—are required for this cellular transformation and subsequent cancer development (carcinogenesis). However, recent evidence suggests that epigenetic modifications—reversible, heritable changes in gene function that occur in the absence of nucleotide sequence changes—may also be involved in carcinogenesis. For example, the addition of methyl groups to a set of genes called stem cell polycomb group target genes (PCGTs; polycomb genes control the expression of their target genes by modifying their DNA or associated proteins) is one of the earliest molecular changes in human cancer development, and increasing evidence suggests that hypermethylation of PCGTs is an epigenetic hallmark of cancer. Why Was This Study Done? The methylation of PCGTs, which is triggered by age and by environmental factors that are associated with cancer development, reduces cellular differentiation and leads to the accumulation of undifferentiated cells that are susceptible to cancer development. It is unclear, however, whether epigenetic modifications have a causal role in carcinogenesis. Here, the researchers investigate the involvement of epigenetic factors in the development of endometrial (womb) cancer. The risk of endometrial cancer (which affects nearly 50,000 women annually in the United States) is largely determined by environmental and lifestyle factors. Specifically, the risk of this cancer is increased in women in whom estrogen (a hormone that drives cell proliferation in the endometrium) is functionally dominant over progesterone (a hormone that inhibits endometrial proliferation and causes cell differentiation); obese women and women who have taken estrogen-only hormone replacement therapies fall into this category. Thus, endometrial cancer is an ideal model in which to study whether epigenetic mechanisms underlie carcinogenesis. What Did the Researchers Do and Find? The researchers collected data on genome-wide DNA methylation at cytosine- and guanine-rich sites in endometrial cancers and normal endometrium and integrated this information with the human interactome and transcriptome (all the physical interactions between proteins and all the genes expressed, respectively, in a cell) using an algorithm called Functional Epigenetic Modules (FEM). This analysis identified HAND2 as the hub of the most highly ranked differential methylation hotspot in endometrial cancer. HAND2 is a progesterone-regulated stem cell PCGT. It encodes a transcription factor that is expressed in the endometrial stroma (the connective tissue that lies below the epithelial cells in which most endometrial cancers develop) and that suppresses the production of the growth factors that mediate the growth-inducing effects of estrogen on the endometrial epithelium. The researchers hypothesized, therefore, that epigenetic deregulation of HAND2 could be a key step in endometrial cancer development. In support of this hypothesis, the researchers report that HAND2 methylation was increased in premalignant endometrial lesions (cancer-prone, abnormal-looking tissue) compared to normal endometrium, and was associated with suppression of HAND2 expression. Moreover, a high level of endometrial HAND2 methylation in premalignant lesions predicted a poor response to progesterone treatment (which stops the growth of some endometrial cancers), and analysis of HAND2 methylation in endometrial secretions collected from women with postmenopausal bleeding (a symptom of endometrial cancer) accurately identified individuals with early stage endometrial cancer. Finally, mice in which the Hand2 gene was specifically deleted in the endometrium developed precancerous endometrial lesions with age. What Do These Findings Mean? These and other findings identify HAND2 methylation as a common, key molecular alteration in endometrial cancer. These findings need to be confirmed in more women, and studies are needed to determine the immediate molecular and cellular consequences of HAND2 silencing in endometrial stromal cells. Nevertheless, these results suggest that HAND2 methylation could potentially be used as a biomarker for the early detection of endometrial cancer and for predicting treatment response. More generally, these findings support the idea that methylation of HAND2 (and, by extension, the methylation of other PCGTs) is not a passive epigenetic feature of cancer but is functionally involved in cancer development, and provide a framework for identifying other genes that are epigenetically regulated and functionally important in carcinogenesis. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001551 The US National Cancer Institute provides information on all aspects of cancer and has detailed information about endometrial cancer for patients and professionals (in English and Spanish) The not-for-profit organization American Cancer Society provides information on cancer and how it develops and specific information on endometrial cancer (in several languages) The UK National Health Service Choices website includes an introduction to cancer, a page on endometrial cancer, and a personal story about endometrial cancer The not-for-profit organization Cancer Research UK provides general information about cancer and specific information about endometrial cancer Wikipedia has a page on cancer epigenetics (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The Eve Appeal charity that supported this research provides useful information on gynecological cancers

Differentiation of endometrial stromal cells into decidual cells is a prerequisite for successful embryo implantation. Our previous studies in the mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is essential for this differentiation process. BMP2 is markedly induced in human primary endometrial stromal cells (HESCs) as they undergo differentiation in response to steroid hormones and cAMP. The present study was undertaken to identify the BMP2-mediated molecular pathways in primary cultures of HESCs during decidualization. Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization. Attenuation of WNT4 expression in HESCs by small interfering RNA administration greatly reduced BMP2-induced stromal differentiation. Additionally, adenovirus-mediated overexpression of WNT4 in HESCs markedly advanced the differentiation program, indicating that it is a key regulator of decidualization. The stimulatory effect of WNT4 was accompanied by the accumulation of active β-catenin in the nuclei of decidualizing stromal cells, indicating the involvement of the canonical WNT signaling pathway. Functional inhibition of WNT4/β-catenin pathway by Dickkopf-1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated silencing of β-catenin expression, greatly reduced the BMP2- and WNT4-induced decidualization. Gene expression profiling revealed that Forkhead box protein O1, a forkhead family transcription factor and previously reported regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. Taken together, these studies uncovered a linear pathway involving BMP2, WNT4/β-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization.

Concerted actions of estrogen and progesterone via their cognate receptors orchestrate changes in the uterine tissue, regulating implantation during early pregnancy. The uterine stromal cells undergo steroid-dependent differentiation into morphologically and functionally distinct decidual cells, which support embryonic growth and survival. The hormone-regulated pathways underlying this unique cellular transformation are not fully understood. Previous studies in the mouse revealed that, following embryo attachment, de novo synthesis of estrogen by the decidual cells is critical for stromal differentiation. In this study we report that Fos-related antigen 1 (FRA-1), a member of the Fos family of transcription factors, is a downstream target of regulation by intrauterine estrogen. FRA-1 expression was localized in the differentiating uterine stromal cells surrounding the implanted embryo. Attenuation of estrogen receptor α (Esr1) expression by siRNA mediated silencing in primary uterine stromal cells suppressed FRA-1 expression. Furthermore, chromatin immunoprecipitation demonstrated direct recruitment of ESR1 to an estrogen response element in the Fra-1 promoter. Down-regulation of Fra-1 expression during in vitro decidualization blocked stromal differentiation and resulted in a marked decrease in stromal cell migration. Interestingly, FRA-1 controls the expression of matrix metalloproteinases MMP9 and MMP13, which are critical modulators of stromal extracellular matrix remodeling. Collectively, these results suggest that FRA-1, induced in response to estrogen signaling via ESR1, is a key regulator of stromal differentiation and remodeling during early pregnancy.

The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2 d/d), the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2 d/d mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy., Author Summary During implantation, various tissue compartments within the uterus, including epithelium and stroma, undergo sequential proliferation and differentiation as the embryo attaches to the uterus and invades into the maternal tissue. There is only limited understanding of the molecular signaling pathways that interconnect these tissue compartments to achieve a functional state of the uterus conducive to implantation. This study reveals that a unique signaling network regulated by the homeobox transcription factors MSX1 and MSX2 in the mouse uterus critically controls female fertility. Targeted mutation of Msx1 and Msx2 genes in female mice, which results in infertility, established that these factors suppress signaling by the morphogenic ligands, WNTS, in the uterus. In the absence of Msx1 and Msx2, the WNT signaling is elevated, leading to the production of a subset of fibroblast growth factors (FGFs) in uterine stroma. These FGFs act in a paracrine manner on the uterine epithelium to promote epithelial proliferation, which results in lack of uterine receptivity and implantation failure. This work, therefore, uncovers an important mechanism in mammalian reproduction and development by identifying key paracrine signals that arise from the uterine stroma to control epithelial function during implantation.

During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.

ZigBee/IEEE 802.15.4 was created to address the market need for a cost-effective, low complexity wireless networking solution that supports low data-rates, low-power consumption in application of short range. In our design, the industry-leading CC2420 from Texas Instruments (TI) is the key single-chip RF transceiver compliant with ZigBee/IEEE 802.15.4. By modifying and trimming the ZigBee stack, a high performance wireless robot network communication system applied in the underground coal mine is designed in this pager.

This paper studies supply chain quality management (SCQM) form a new perspective of immune theory, which is borrowed from the research achievements of biology. Firstly, we introduce the concept of SCQM, analyzing the similarities between SCQM system and the immune system. Secondly , we summarize and analyze the four aspects of the immune: recognition, learning, memory, effects. Thirdly, we integrate the relevant elements of the immune system into the SCQM system to propose a SCQM model based on immune theory by analyzing the mechanisms and functions from the four aspects. Finally, we discuss the managerial implications and future directions for the models.

During early pregnancy, the concerted actions of the maternal steroid hormones, estrogen and progesterone, promote a unique process known as decidualization, which involves extensive proliferation and differentiation of uterine stromal cells. The molecular pathways underlying this hormonally induced cellular transformation, an essential prerequisite for embryo implantation, remain poorly understood. We previously identified CCAAT/enhancer binding protein beta (C/EBPbeta) as a target of steroid regulation in the uterus. Uteri of mice lacking C/EBPbeta failed to undergo decidualization. In the present study, analyses of C/EBPbeta-null uteri indicated that loss of this factor leads to a block in stromal cell proliferation in response to a decidual stimulation. The mutant stromal cells entered S phase of the cell cycle and completed DNA synthesis but were unable to execute mitosis. Further analysis revealed that C/EBPbeta facilitates the transition of these cells into mitosis by binding directly to the cyclin B2 promoter to regulate its expression. The expression of cdc25C, a phosphatase that maintains the active state of the cyclin B-cyclin-dependent kinase complex during mitosis, is also strongly suppressed in C/EBPbeta-null stromal cells. Furthermore, the expression of the tumor suppressor p53 and the cell cycle inhibitors p21 and p27 was markedly elevated in C/EBPbeta-null stromal cells before the mitotic phase, uncovering additional mechanisms by which C/EBPbeta controls G2 to M transition. Collectively, these results revealed that C/EBPbeta mediates the effects of steroid hormones during decidualization by modulating the expression of multiple key cell cycle regulatory factors that control the G2 to M transition of the proliferating uterine stromal cells.

This paper comprehensive analyzed the key factors of regional logistics development. On the basis of these, the evaluation index system of regional logistics development was established. Then the measuring model was proposed based on the AHP, and the six typical regions were chosen as the evaluation objects. Finally, according to the evaluation results, a brief analysis was given and suggestions were presented.

In this paper, the video sever system is designed centered on IME6410. Based on the platform of embedded processor and Linux, after analyzing the internal relations among Video4Linux(V4L) specification, video driver and kernel of Linux, we proposea common method for driver development accord with V4L Specification

Flexibility has been considered as a major determinant of competitiveness in an increasingly intense competition in the marketplace. Effective control of supply chain flexibility can improve the supply chain and business performance. Thus, it is necessary to assess supply chain flexibility precisely and systematically. This paper gives a considerable comprehensive analysis of supply chain flexibility and identifies five elements of supply chain flexibility, including operation flexibility, logistics flexibility, information flexibility, robust network and re-configuration flexibility, market and supply flexibility. According to the characteristics of supply chain flexibility, this paper develops a new framework for assessing supply chain flexibility. Based on the limited existing literatures, a dynamic synthetic evaluation model is presented to assess supply chain flexibility, which introduces time parameters to the evaluation model and gives consideration to the functionality and proportionality of the evaluation index. Finally, a numerical example is presented for the illustration of the proposed methodology. This paper builds on the theoretical foundation and leads to more effective formulation of supply chain strategies.

Based on the viewpoints of synergistic theory and the concept of coupling and coordination, this paper establishes coupling coordination degree model of interaction between upstream and downstream enterprises. Furthermore, it puts forward coupling coordination degree model which includes efficacy function, coupling degree function, coupling coordination degree function. This paper also establishes and analyses indicator system of enterprises relationship on the basis of an example,analyses the development and change of the coupling between upstream and downstream enterprises, and provides quantitative decision-making basis in order to maintain and improve partnership. Finally, it proposes some suggestions for the future research. Scientific and reasonable evaluation of interaction between upstream and downstream enterprises contributes to the improvement of relationship. Many scholars have conducted a lot of qualitative and quantitative researches on upstream and downstream enterprises. Results of this paper show that it is reasonable to evaluate interaction between upstream and downstream enterprises with coupling and coordination degree model.

China?s current real estate development is very fiery, but there are also many problems, including a higher incidence of complaints, lower customer satisfaction and loyalty. How to effectively solve these problems to fundamentally ensure their healthy and lasting development is crucial. At present, academic papers on the real estate are more associated with the policy, and most are the qualitative research articles. This paper focuses on the current social issues, through the empirical analysis, to study the relationships among customer participation, customer satisfaction and customer loyalty in real estate industry. Suggestions for real estate firms and government are discussed at the end.

The research on supply chain partnership is one of important areas of supply chain. The relationship between partners has a great impact on the success of supply chain. This paper analyzes many factors influencing the relationship quality of supply chain partners, applies the fuzzy comprehensive evaluation to the relationship quality based on fuzzy mathematics theory, combines the empirical data to evaluate the relationship level of supply chain partners, establishes the factor sets, the evaluation sets and the weight sets, and makes the evaluation of the weight sets by AHP to avoid the effect of individual subjective judgment and favoritism on the result of relationship quality evaluation of supply chain partners. This paper attempts to provide a qualitative and quantitative analysis for studying the relationship quality of supply chain partners, and the results show that the method of fuzzy comprehensive evaluation can be used widely in the researches on supply chain partners.

Market is undergoing the globalization that makes some enterprises associate with each other so as to enhance their competitive competency. The future competition among enterprises has already evolved into the competition among supply chains, and thus supply chain partnership appears. It's a complex process to manage the supply chain partnership and establish a long-term and steady strategic cooperative partnership. This paper summarizes almost one hundred current researches on supply chain relationship, and divides the management of supply chain partnership into four stages- demand analysis, collection of partner information, partner selection and partner tracking management. It analyzes the advances in research of the management of supply chain relationship, and further points out the insufficiencies in the current researches. Finally, it proposes some prospects on research direction of the management of supply chain partnership.

To collaborate with the distributed grid services, sustain the dynamic computing environment and satisfy variable user demands, this paper proposes the concept of cooperative intelligent grid (CIG) and discusses its architecture. In CIG, the cooperative logic is apparently expressed and separates from computing logic. From three aspects: policy-driven system frame in the form of community/federation, role-based medium service, rational negotiation mechanism, this paper constructs an open, dynamic, no obvious overall control infrastructure. Meanwhile, this paper differently gives a domain-adaptive grid service composition algorithm, and a rational negotiation algorithm referring to the reasoning method of BDI Agent.

The steroid hormone progesterone (P) plays a pivotal role during ovulation. Mice lacking P receptor (Pgr) gene fail to ovulate due to a defect in follicular rupture. The P receptor (PGR)-regulated pathways that modulate ovulation, however, remain poorly understood. To identify these pathways, we performed gene expression profiling using ovaries from mice subjected to gonadotropin-induced superovulation in the presence and in the absence of CDB-2914, a synthetic PGR antagonist. Prominent among the genes that were down-regulated in response to CDB-2914 was endothelin (ET)-2, a potent vasoactive molecule. ET-2 mRNA was transiently induced in mural granulosa cells of the preovulatory follicles immediately preceding ovulation. This induction was absent in the ovaries of PGR null mice, indicating a critical role of this receptor in ET-2 expression. To investigate the functional role of ET-2 during ovulation, we employed selective antagonists of endothelin receptors, ETR-A and ETR-B. Mice treated with an ETR-B antagonist exhibited a dramatic (>85%) decline in the number of released oocytes. Strong expression of ETR-B was observed in the mural and cumulus granulosa cells of the preovulatory follicles as well as in the capillaries lining the inner border of the theca interna. We also identified cGMP-dependent protein kinase II, a previously reported PGR-regulated gene, as a downstream target of ET-2 during ovulation. Collectively, our studies uncovered a unique pathway in which ET-2, produced by PGR in mural granulosa cells, acts in a paracrine or autocrine manner on multiple cell types within the preovulatory follicle to control the final events leading to its rupture.

Previous studies indicated that calcitonin (CT), a peptide hormone involved in calcium (Ca2+) homeostasis, is transiently induced by steroid hormone progesterone (P) in the uterine epithelia of the rat and human within the window of implantation. Targeted disruption of uterine CT expression markedly impaired implantation in the rat. To gain insight into the molecular events underlying CT action in the endometrium, we performed gene expression profiling in response to CT in a human endometrial adenocarcinoma cell line, Ishikawa. We identified the gene encoding tissue tranglutaminase type II (tTGase), which participates in Ca2+-dependent, protein-protein cross-linking, as a downstream target of CT. Interestingly, addition of P alone to Ishikawa cells led to a marked induction in the level of both CT and tTGase, indicating the existence of a pathway involving P receptors, CT, and tTGase in these cells. Other studies revealed that regulation of the tTGase gene by CT occurs via its cell surface receptor and uses both cAMP and Ca2+ signaling pathways. We also noted that tTGase protein is expressed in human endometrium during the P-dominated midsecretory phase of the menstrual cycle, and it is localized at the basal membrane of glandular epithelium and the surrounding stroma. The spatio-temporal expression of tTGase in human endometrium during the cycle closely overlapped with that of CT. In summary, we have uncovered a novel steroid-regulated signaling cascade in which P induces CT, which, in turn, induces tTGase and potentially plays a critical role in the human endometrium during implantation.

During early pregnancy, steroid hormones estrogen (E) and progesterone (P) regulate a complex series of interactions between the implanting embryo and the uterus by controlling the proliferation and differentiation of uterine epithelium and stroma in a timely manner. To identify the steroid-regulated genes that control these functions, we performed messenger RNA profiling of mouse uterine tissues at the time of implantation. Our analysis revealed that the expression of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is rapidly induced in the pregnant uterus at the time of blastocyst attachment. The expression of C/EBPbeta increased further during the decidualization phase of pregnancy and was localized in the proliferating as well as the decidualized stromal cells surrounding the implanted embryo. Administration of E or P to ovariectomized females induced C/EBPbeta expression in both uterine epithelium and stroma, showing a dual regulation of this gene by these hormones. The female C/EBPbeta-null mice are infertile. We, therefore, assessed steroid-hormone-dependent responses in the uteri of these mice. We observed that E-induced proliferation of uterine epithelial cells is markedly compromised in the absence of C/EBPbeta. Most strikingly, there was a complete lack of response of the C/EBPbeta-deficient uteri to an artificial deciduogenic stimulus, indicating a critical role of this transcription factor in regulating the decidualization program. Further analysis revealed defects in steroid-induced stromal cell proliferation and differentiation in C/EBPbeta-null uteri. Collectively, our studies established that C/EBPbeta is a key mediator of steroid responsiveness of the epithelium and stroma in the mouse uterus.

The steroid hormone progesterone (P) is a critical regulator of embryo implantation and maintenance of pregnancy. P acting through the nuclear progesterone receptors (PRs) regulates the expression of specific gene networks that in turn control the extensive cell proliferation, differentiation, and remodeling that occur in various uterine cell types during the progressive phases of implantation. To identify the P-regulated pathways that underlie the implantation process in the mouse, we employed RU 486, a well-characterized PR antagonist that binds to the receptor and blocks its gene regulatory function. We performed messenger RNA (mRNA) profiling in the peri-implantation uterus using oligonucleotide microarrays to analyze changes in mRNA levels in response to RU 486. This analysis provided, for the first time, a comprehensive profile of PR-regulated gene networks with potential roles during implantation. Our study identified a variety of novel PR-regulated molecules, such as growth factors, protease inhibitors, metabolic enzymes, peptide hormones, transcription factors, immune response molecules, cytoskeletal proteins, and cell adhesion molecules, that are potential mediators of P action in the peri-implantation mouse uterus. This article provides a brief description of the expression and function of these newly identified molecular pathways.

The cellular actions of steroid hormone progesterone (P) are mediated via its nuclear receptors, which regulate the expression of specific target genes. The identity of gene networks that are regulated by the P receptors (PRs) in the uterus at various stages of the reproductive cycle and pregnancy, however, remain largely unknown. In this study, we have used oligonucleotide microarrays to identify mRNAs whose expression in the pregnant mouse uterus is modulated by RU486, a well-characterized PR antagonist, which is also an effective inhibitor of implantation. We found that, in response to RU486, expression of mRNAs corresponding to 78 known genes was down-regulated at least 2-fold in the preimplantation mouse uterus. The PR regulation of several of these genes was ascertained by administering P to ovariectomized wild-type and PR knockout (PRKO) mice. Detailed spatio-temporal analysis of these genes in the pregnant uterus indicated that their expression in the epithelium and stroma could be correlated with the expression of PR in those cell types. Furthermore, time-course studies suggested that many of these genes are likely primary targets of PR regulation. We also identified 70 known genes that were up-regulated at least 2-fold in the pregnant uterus in response to RU486. Interestingly, initial examination of a number of RU486-inducible genes reveals that their uterine expression is also regulated by estrogen. The identification of several novel PR-regulated gene pathways in the reproductive tract is an important step toward understanding how P regulates the physiological events leading to implantation.

Previous studies indicated that calcitonin (CT), a peptide hormone involved in calcium homeostasis, is transiently expressed in the receptive rat and human endometrial epithelia within the window of implantation. Attenuation of uterine CT expression using antisense methods severely impaired implantation in the rat. The molecular pathway of CT in the pregnant uterus, however, remains unknown. In the present study, we investigated the cellular events following the binding of CT to its membrane receptors in human endometrial epithelial cell line Ishikawa. We observed that CT treatment triggers a transient rise in intracellular calcium in these cells. Most interestingly, CT treatment also led to the disappearance of E-cadherin, a critical cell adhesion molecule, from cell-cell contact sites. Blockade of intracellular calcium release by BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl) prevented the CT-induced disappearance of E-cadherin. Our studies further revealed that CT treatment markedly down-regulates the level of E-cadherin mRNA in Ishikawa cells. We also examined whether CT influences the expression of E-cadherin mRNA in intact rat uterine tissue during implantation. In pregnant rats, high levels of E-cadherin mRNA were expressed during the first 3 days of gestation when the CT mRNA in uterine epithelial cells is undetectable. Concomitant with a transient burst of CT expression during days 4–5 of pregnancy, the level of E-cadherin mRNA declined sharply. Furthermore, administration of exogenous CT to animals on day 2 of pregnancy led to a premature suppression of E-cadherin mRNA level on day 3, indicating a direct link between elevated levels of uterine CT and the down-regulation of E-cadherin expression in the surface epithelium. Collectively, our results are consistent with the hypothesis that CT-induced reduction in E-cadherin expression may remodel the adherens junctions between epithelial cells, and this change in epithelial cell phenotype might be a critical event during the implantation of the blastocyst.

The steroid hormone estrogen profoundly influences growth and differentiation programs in the reproductive tract of cycling and pregnant mamals. It is thought that estrogen exerts its cellular effects by regulating the expression of specific target genes. We utilized a messenger RNA differential display method to identify the genes whose expression is modulated by estrogen in the preimplantation rat uterus. Here we report the cloning of a novel gene (ERG1) that is tightly regulated by estrogen in two key reproductive tissues, the uterus and oviduct. Spatio-temporal analyses reveal that ERG1 mRNA is expressed in a highly stage-specific manner in the uterus and oviduct, and its expression is restricted to the surface epithelium of both of these tissues. Nucleotide sequence analysis of the full-length ERG1 cDNA indicates that it has an open reading frame of 1821 nuceotides encoding a putative protein of 607 amino acids with a single transmembrane domain and a short cytoplasmic tail. The extracellular part of the protein contains several distinct structural motifs. These include a zona pellucida binding domain, which is present in a number of proteins such as the zona pellucida sperm binding proteins, and uromodulin, In addition, there is a repeat of a motif called CUB domain, which exists in a number of genes involved in development and differentiation such as bone morphogenetic protein 1 (BMP1). Although the precise function of ERG1 eludes us presently, its unique pattern of expression in the uterus and oviduct and its regulation by estrogen, a principal reproductive hormone, lead us to speculate that this novel gene plays an important role in events during the reproductive cycle and early pregnancy.