Apoptosis in normal and neoplastic mammary gland development

Apoptosis plays important roles in mammary development from early embryonic formation of the mammary gland to the regression that follows cessation of cycling. The most dramatic occurrence of apoptosis is found during mammary involution. Most of the secretory epithelium in the lactating breast undergoes apoptosis as the mammary gland regresses and is reorganized for another cycle of lactation. We used the morphology, biochemical changes, and gene expression detected in apoptotic mammary epithelium during involution as a model for studying cell death during other stages of mammary development and for approaching the failure of apoptosis found in mammary hyperplasia. Morphological studies and gene expression have suggested that apoptosis during involution is comprised of two phases: an early limited apoptosis in response to hormone ablation and later protease promoted widespread apoptosis in response to altered cell-matrix interactions and loss of anchorage. We examined protein expression during involution for changes associated with loss of hormone stimulation and altered cell-matrix interactions. One of the proteins whose expression is able to inhibit apoptosis, and is altered during mammary epithelial cell was the serine-threonine protein kinase, Akt 1. Akt 1 activation is common to hormone, growth factor, and anchorage-mediated survival of epithelial cells. We found regulated expression of activated Akt 1 in the mammary gland during involution. Akt 1 activation peaked in pregnancy and lactation, and decreased significantly during apoptosis in mammary involution. Mechanisms of Akt 1 action include modulation of the ratio bcl-2 family members implicated in control of apoptosis. Bcl-2 family proteins were also expressed in pattern consistent with Akt 1 regulation. These observations led us to examine expression of activated Akt 1 and bcl-2 family proteins in premalignant hyperplasias. Akt 1 activation was increased; expression of anti-apoptotic proteins bcl-2 and bcl-x was strongly increased while pro-apoptotic bax was greatly diminished in three different lines of transplantable premalignant mammary hyperplasia. This data suggest that activation of Akt 1 by hormone- or anchorage-mediated pathways regulates survival of mammary epithelium and can contribute to initiation of neoplasia. These data suggest that perturbation of normal cell turnover can contribute to initiation of neoplasia.     

Second-order stereology of benign and malignant alterations of the human mammary gland

The purpose of the present study was a quantitative characterization of the three-dimensional arrangement of the epithelial component of benign and malignant alterations of the female breast by combining stereology with stochastic geometry. Twenty cases of fibrous mastopathy and 20 cases of invasive ductal mammary cancer were studied at the light microscopic level. Segmentation of the epithelial tissue component was performed with an image analyser. From the resulting binary images, unbiased estimates of the covariance C(r) and the intensity V_v of the epithelial volume component were obtained automatically by computer. From these data, estimates of the correlation function k(r), of the pair correlation function g(r), of the radial distribution function RDF(r) and of the reduced second moment function K(r) of epithelial volume were determined. The estimates of C(r) and RDF(r) differed between groups, but these functions depend on spatial pattern and V_v. As carcinomas showed a significantly higher epithelial volume density V_v than mastopathies, estimation of C(r) and RDF(r) alone did not permit a safe distinction between possibly different types of spatial arrangement of epithelium in the benign and malignant lesions. Analysis of the estimates of k(r), g(r) and K(r), which are not influenced by V_v, showed definite interaction between epithelial volume elements, with clustering at short distances and repulsion at long distances. In both groups, the null hypothesis of purely random arrangement of epithelium had to be rejected. The clearest distinction between groups was obtained by estimation of g(r), which showed that short-range, tubular pattern as well as long-range, lobular architecture are better preserved in benign than in malignant lesions. The low interindividual scatter of k(r), g(r) and K(r) indicates a high biological significance of spatial pattern, which is presumably under strict genetic control. Potential uses of the method are: (i) the identification of biomathematical models which could contribute to a better understanding of the growth processes involved, (ii) conditional simulation of the underlying three-dimensional structures by computer, and (iii) supporting the diagnosis of mammary lesions with borderline histopathological appearance.     

基于ECD下的轿车塑料油箱生命周期实现及探讨

在阐述环境意识设计(ECD)的实现目标及方法的基础上，结合轿车塑料油箱产品的实例，进行了全生命周期的ECD实现，并作了初步的分析及探讨。     

Manufacturing mode selection in knowledgeable manufacturing during product life cycle

Despite certain unpredictable factors, a mapping relationship can be constructed between the manufacturing mode and the characters of product life cycle (PLC). The PLC data and the corresponding manufacturing modes of similar products can be stored in a chronological knowledge base for later reference or application, thereby providing a reliable basis for the selection of optimal manufacturing modes for new products. Product demand, production lead time and inventory are defined as the PLC characters, which can be approximated by unimodal or antiunimodal functions. The approximate matching functions, whose monotonicity and ranges are demonstrated by the proofs of propositions 1–3, are constructed to normalize the PLC characters and match the sample data of the new product with those of the original. Three algorithms for clustering, approximate matching and re-matching are proposed for the matching of the characteristic values of a new product with those of a similar one in the knowledge base for optimal mode selection. The validity of this method has been tested by a practical example.     

Protein kinases in mammary gland development and cancer

Protein kinases, the enzymes responsible for phosphorylation of a wide variety of proteins, are the largest class of genes known to regulate growth, development, and neoplastic transformation of mammary gland. Mammary gland growth and maturation consist of a series of highly ordered events involving interactions among several distinct cell types that are regulated by complex interactions among many steroid hormones and growth factors. The mammary gland is one of the few organ systems in mammals that complete their morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. Thus, the mammary gland is an excellent model for studying normal development and the early steps of tumor formation. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy. Numerous experimental and epidemiological studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression and functions of protein kinases. Perturbations in the regulated expression or function of protein kinases or their associated signaling pathways can lead to malignant transformation of the breast. For example, overexpression of several receptor-tyrosine kinases, including human epidermal growth factor receptor and HER2/Neu, has been shown to contribute to the development of breast cancer. Since receptor-tyrosine kinases regulate several essential processes such as mitogenesis, motility, invasion, cell survival, and angiogenesis, targeting receptor-tyrosine kinases may have important implications in designing strategies against breast cancer.     

Cancer risk related to mammary gland structure and development

The breast undergoes dramatic changes in size, shape, and function in association with growth, reproduction, and post-menopausal regression. Those changes impact women's lifetime breast cancer risk. An early first full-term pregnancy exerts a protective effect, emphasizing the need for understanding the role of reproductive influences on breast development and on cancer initiation and progression, and providing a paradigm for developing preventive strategies based on physiological principles. Even though the cause of breast cancer and the ultimate mechanisms through which an early pregnancy protects from cancer development remain largely unknown, a likely explanation for this protection has been provided by experimental in vivo and in vitro models. These studies have led to the conclusions that cancer initiation requires the interaction of a carcinogen with an undifferentiated and highly proliferating mammary epithelium, whereas differentiation of the mammary gland inhibits carcinogenic initiation. The process of mammary gland differentiation is the result of complex interactions of ovarian, pituitary, and placental hormones, which in turn induce inhibition of cell proliferation, downregulation of estrogen and progesterone receptors, activation of specific genes, such as inhibin, mammary derived growth factor inhibitor and a serpin-like gene, and expression of extracellular matrix proteins in the normal breast. Cell immortalization and transformation are associated with the expression of ferritin H and S100P protein, which serve as markers of cancer initiation. Comparative studies of normal and neoplastic breast development have unraveled similarities with experimental models that validate the extrapolation of findings for testing hypotheses on the initiation and progression of breast cancer.     

Sustainable manufacturing,life cycle thinking and the circular economy

Achieving sustainable pattems of consumption and production is perhaps the biggest chaLlenge facing our society today. The de-mand for more safe environmentally benign products is rising and many companies are looking for new ways to progressively improve the sus-tainability of their products. Moreover, there are numerous opportunities and countless innovations, technological as well as non-technologi-cal, that need to be exploited to improve the sustainability of products. Manufacturing industry is an important sector of any economy and has the potential to become a driving force for enabling sustainable pattems of production and consumption through introducing efficient production practices and developing products and services that help reduce environmental impacts. The benefits of adopting an integrated policy towards product development based on life cycle thinking and eco-design to stimulate improvement of the environmental performance of each part of product life cycle phases and achieve sustainable pattems of production and consumption are emphasized. The challenges in implementing sustainable manufacturing and the circular economy approaches are listed. A number of solutions are suggested to face up these challenges, for instance, increased awareness of enterprises particularly SME's of product life cycle issues and the opportunities that are available for cost savings and profit making from eco-innovation in product development for both the domestic and export markets and providing practical help and advice directly to enterprises on integrated product development to promote enterprise led Eco-innovation. Aiming at contributing to sus-tainable manufacturing in China, Sino-UK Low Carbon Manufacturing Consortium, a multi-disciplinary research and educational partnership between academia, industry and govemment agencies in the UK and China with interest in sustainable manufacturing issues, has been formed recently. The vision, aims and benefits of membership of the consortium are also discussed.     

Intracellular localization of samarium in the lactating mammary gland cells: ultrastructural and microanalytical study

The frequent use of some rare earths in the medical and industrial domains make us worry about their intracellular behavior into the body. Reason for which we have investigated the subcellular localization of one of these elements, the samarium, in the mammary gland of lactating female wistar rats using two very sensitive methods of observation and microanalysis, the transmission electron microscopy and the secondary ion mass spectrometry. The ultrastructural study showed the presence of electron dense deposits in the lactating mammary glandular epithelial cell lysosomes of the samarium-treated rats, but no loaded lysosomes were observed in those of control rats. The microanalytical study allowed both the identification of the chemical species present in those deposits as samarium isotopes ((152) Sm(+)) and the cartography of its distribution. Our results confirm the previous ones showing that lysosomes of the glandular epithelial cells are the site of the intracellular concentration of foreign elements such as gallium. The intralysosomal deposits observed in the mammary glandular cells of the samarium-treated rats are similar in their form and density to those observed with the same element in other varieties of cells, such as liver, bone marrow, and spleen cells. Our ultrastructural and microanalytical results and those obtained in previous studies allow deducing that the intralysosomal deposits are very probably composed of an insoluble samarium phosphate salt.     

乳腺慢性炎症X线、MRI影像分析

目的 :分析乳腺慢性炎症的X线、MRI表现,提高其诊断正确率。方法:回顾性分析26例病理或临床证实为乳腺炎患者的临床资料、乳腺X线和MR资料。结果:慢性乳腺炎主要发生在乳晕后方及周围,X线表现可分为致密型、结节型、肿块型及混合型四型。MRI病灶于T1WI呈低或等信号,T2WI呈高或等高信号,增强后病灶全部明确显示,其中区域样强化42.3%(l1/26),局灶性强化11.5%(3/26),肿块样强化7.7%(2/26),弥漫性强化7.7%(2/26),集簇环状强化30.8%(8/26);26例中,时间-信号强度曲线呈I型、Ⅱ型和Ⅲ型的百分比依次为73.1%、19.2%和7.7%;MRI诊断乳腺炎的误诊率为7.7%(2/26)。结论:区域样分布的病变呈多发簇环状强化和增强后动态曲线呈I型或II型是乳腺慢性炎症较常见的MRI表现,对乳腺炎的检出和定位诊断具有较大的临床价值,诊断需密切结合临床。     

产品生命周期管理与制造业信息化

产品生命周期管理技术注重对各类产品全生命周期的管理,注重与ERP/SCM/CRM等软件系统的集成,既能成为制造业的产品数据管理平台,也能成为各类信息化软件系统的集成平台,是解决制造业中“信息孤岛”问题的有效方法。主要介绍PLM的内涵和体系结构,并探讨PLM在制造业信息化过程中系统集成问题。     

再制造发动机全生命周期评估

以再制造发动机为研究对象,运用生命周期评价（LCA）方法,评估再制造发动机的生命周期指标,从能源、原材料和环境三方面评价发动机再制造工程,并通过实际案例说明了生命周期评价在再制造发动机方面的应用。研究结果表明：同制造一台新发动机相比,再制造一台发动机可以节省58．2kg的钢材,16kg的铝材,节约113kWh的电能,可以减少565kg的CO2排放,6．09kg的CO排放,1．01kg的NOx排放,3．985kg的SOx排放,同时可以减少288．725kg的固体废弃物排放。再制造发动机具有极大的经济性和实用性。     

企业生命周期理论与企业管理创新

通过对企业生命周期理论及其各个阶段不同特点的详细论述，提出了国内企业实现管理创新的具体思路。     

3D reconstruction of histological sections: Application to mammary gland tissue

In this article, we present a novel method for the automatic 3D reconstruction of thick tissue blocks from 2D histological sections. The algorithm completes a high‐content (multiscale, multifeature) imaging system for simultaneous morphological and molecular analysis of thick tissue samples. This computer‐based system integrates image acquisition, annotation, registration, and three‐dimensional reconstruction. We present an experimental validation of this tool using both synthetic and real data. In particular, we present the 3D reconstruction of an entire mouse mammary gland and demonstrate the integration of high‐resolution molecular data. Microsc. Res. Tech. 73:1019–1029, 2010. © 2010 Wiley‐Liss, Inc.     

基于生命周期的产品成本效益分析及支持系统设计

成本效益分析是企业经营管理活动中非常重要的环节。本文从产品市场生命周期和产品价值链生命周期两个方面,提出了产品成本效益分析系统功能,并研究了用于成本效益分析的信息支持系统的集成方法。     

再制造发动机寿命周期费用分析

运用寿命周期费用理论对再制造发动机进行分析,通过实例得到某型号再制造发动机的经济寿命,并将其与新机进行比较,所得结论对企业的设备管理具有一定的参考价值。     

产品生命周期集成技术研究现状及发展趋势

分析了产品生命期集成技术研究现状,指出了存在的问题,论述了今后研究的发展趋势。     

面向过程的产品数据生命周期管理

借鉴统一建模语言(UML)描述类对象生命周期的方法,基于对产品数据对象的生命周期分析,引出了生命周期状态机的概念,提出了面向过程的产品数据生命周期管理策略,最后,建立了面向过程的产品数据生命周期管理模型,并对其进行了详细分析。