Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following formation of a micrometastatic tumour mass by inhibiting metastatic processes including angiogenesis, bone remodeling and immunosuppressive cell functions. In this review we will highlight some of the mechanisms mediating DTC dormancy and the complex relationships which occur between tumor cells and bone resident cells in the bone metastatic microenvironment. These inter-cellular interactions may be important targets to consider for development of novel effective therapies for the prevention or treatment of bone metastases.     

Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.     

零压挤出

为满足用户日新月异的需求 ,多年来人们致力于挤出机技术的改进工作。最简单的就是热喂料挤出机 ,它最多只能称作是在一个圆筒内工作的阿基米德螺杆 ,通常用来将没有定型的不连续的胶料制成一定横截面和尺寸均一的连续胶条。但是不能小看这种装置 ,这种古老的热喂料挤出机是很有用的 ,它可以生产轮胎零部件和其它许多工业橡胶制品 ,包括胶带和胶管。至今仍有许多热喂料挤出机在使用中。冷喂料挤出机代替热喂料挤出机有几个很重要的原因 ,其中之一就是热喂料挤出机要求母炼胶充分预热 ,而热炼机费用极为昂贵 ,而且这些价格不菲的庞大装置占地…     

Public Key Cryptography in Action

This article discusses data security and controls, primarily in the context of data base management systems (DBMSs), with an emphasis on basic principles and mechanisms that have been successfully used by practitioners in actual products and systems. The general discussion does not focus on particular products, although a later section does review several products to illustrate previously discussed concepts. The discussion of data bases is limited specifically to relational DBMSs, which store data in relations that have specific mathematical properties. All examples given are in SQL. It is assumed that readers are familiar with rudimentary concepts of relational data bases and SQL.

This article begins with a review of basic security objectives, followed by a discussion of access controls in the current generation of commercially available DBMSs. The problem of multilevel security is then introduced, including a review of techniques developed specifically for multilevel security.     

Wire + Arc Additive Manufacturing

Depositing large components (>10?kg) in titanium, aluminium, steel and other metals is possible using Wire + Arc Additive Manufacturing. This technology adopts arc welding tools and wire as feedstock for additive manufacturing purposes. High deposition rates, low material and equipment costs, and good structural integrity make Wire+Arc Additive Manufacturing a suitable candidate for replacing the current method of manufacturing from solid billets or large forgings, especially with regards to low and medium complexity parts. A variety of components have been successfully manufactured with this process, including Ti–6Al–4V spars and landing gear assemblies, aluminium wing ribs, steel wind tunnel models and cones. Strategies on how to manage residual stress, improve mechanical properties and eliminate defects such as porosity are suggested. Finally, the benefits of non-destructive testing, online monitoring and in situ machining are discussed.     

MeeGo：将开源进行到底

MeeGo,正在成为移动直联网领域的一颗新星。 在今年2月的世界3GSM大会上,诺基亚与英特尔一起宣布了新一代专门针对移动终端的智能操作平台——MeeGo的诞生。MeeGo是英特尔的Moblin与诺基亚的Maemo的组合体,是为下一代计算设备打造的基于Linux系统的开源软件平台,它完全开放源代码,能够将服务、内容与用户体验相结合,为消费者带来全新的移动互联的操作体验。目前MeeGo由国际非盈利性组织Linux基金会进行管理。     

The Shopping Jacket: Wearable computing for the consumer

As part of the Bristol Wearable Computing Initiative, we are exploring location-sensing systems suitable for use with wearable computing. In this paper we present our findings, and in particular a wearable application — the ‘Shopping Jacket’ — which relies on a minimal infrastructure to be effective. We use two positioning devices, ‘pingers’ and GPS. The pinger is used to signal the presence of a shop, and to indicate the type of shop and its website. The GPS is used to disambiguate which branch of a high street chain is being passed. The wearable uses this information to determine whether the wearer needs to be alerted that they are passing an interesting shop, or to direct the wearer around a shopping mall. The Shopping Jacket integrates a wearable CardPC, GPS and pinger receivers, a near-field radio link, hand-held display, GSM data telephone and a speech interface into a conventional sports blazer.     

Euclidean controllable realizations of linear hereditary systems

A realization problem for a class of linear hereditary systems is formulated and state space representations are constructed from inputoutput relations. The resulting hereditary models are shown to be Euclidean controllable, and comparisons are made between these hereditary realizations and other recently developed theories.This research was supported in part by the Air Force Flight Dynamics Laboratory under grant AFOSR-77-3221.