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.     

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.     

Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.     

Exponential increases of the brominated flame retardants,polybrominated diphenyl ethers,in the Canadian Arctic from 1981 to 2000

A suite of 37 polybrominated diphenyl ether (PBDE) congeners and all of the homologue groups from mono- to deca-brominated were determined in ringed seal (Phoca hispida) blubber collected from subsistence hunts in the Canadian Arctic in 1981, 1991, 1996, and 2000. Total PBDE (sum(PBDE)) concentrations have increased exponentially over this period in male ringed seals aged 0-15 years. Penta- and hexa-BDEs are increasing at approximately the same rate (t2 = 4.7 and 4.3 years, respectively) and more rapidly than tetra-BDEs (t2 = 8.6 years) and tri-BDEs (t2 = infinity) in this age/sex grouping. In contrast to declining PBDE concentrations since 1997 in human milk from Sweden, sum(PBDE) concentrations in arctic ringed seals continue to increase exponentially similar to worldwide commercial penta-BDE production. PBDE congener profiles in male ringed seals aged 0-15 years from 1991 to 2000 also differ significantly from other aquatic organisms and semipermeable membrane devices collected from temperate coastal regions of British Columbia. While PBDE concentrations are 50 times lower than those of mono-ortho and non-ortho PCBs, and approxiamately 500 times higher than PCDD/Fs, our data indicate that, at current rates of bioaccumulation, PBDEs will surpass PCBs to become the most prevalent organohalogen compound in Canadian arctic ringed seals by 2050.     

Removal of organochlorine pesticides and polychlorinated biphenyls from marine oils during refining and hydrogenation for edible use

Raw marine oils containing from 2–8 ppm DDT group pesticides, 0.00–0.03 ppm dieldrin, and 3–13 ppm polychlorinated biphenyls (as Aroclor 1254) were subjected to pilot plant refining, hydrogenation, and deodorization for margarine stock production. Residues of all 3 groups were reduced to below detectable limits (0.06 ppm, 0.01 ppm, and 0.5 ppm for ΣDDT, dieldrin, and polychlorinated biphenyls [determined as decachlorobiphenyl], respectively) as a result of processing.     

Individual hemisphericity and maladaptive behaviors.

Individual hemisphericity of 13 nonparanoid schizophrenics, 12 depressives, 20 manic-depressives, 5 schizo-affectives, 25 alcoholics, and 25 Ss with personality disorders (antisocial type) was compared by utilizing the conjugate lateral eye-movement index. In the population of 100 right-handed males, 45% were found with right hemisphericity, 41% with bilaterality, and 14% with left hemisphericity. Right hemisphericity was found associated with nonparanoid schizophrenia, depression, and alcoholism; bilaterality was found to be related to manic-depression, schizo-affective disorder, and antisocial personality. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)