MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia

Prior studies have identified Fibroblast Growth Factor-8 (Fgf8) as a possible proto-oncogene in mouse mammary tumorigenesis. We now report on the generation of two types of Fgf8 transgenic mice that each utilize the mouse mammary tumor virus (MMTV) promoter. The first transgene (MMTV-Fgf8b) results in the overexpression of the FGF8b isoform exclusively. Male and female MMTV-Fgf8b transgenic mice are viable and fertile. RNA for FGF8b is detected in mammary gland and salivary gland tissues of transgenic mice by Northern blot analysis. Nearly 85% of breeding transgenic female mice developed mammary lobular adenocarcinomas by 12 months of age, while no tumors developed in non-transgenic littermates. Salivary gland tumors occurred in some animals, always in association with mammary tumors. Several MMTV-Fgf8b transgenic mice had lung metastases at necropsy. The second transgene (MMTV-Fgf8) uses the entire Fgf8 gene and potentially encodes all FGF8 isoforms. Fgf8 is expressed by this transgene in several tissues in addition to those described above, notably the ovaries. The two MMTV-Fgf8 founders developed mammary ductal adenocarcinomas at five and eight months of age, and both displayed ovarian stromal hyperplasia. The founders expressing either transgene did not successfully nurse their pups. These results demonstrate that production of FGF8b, and possibly other FGF8 isoforms, in the mammary and salivary glands contributes to oncogenesis, and that ovarian expression results in stromal hyperplasia.     

Major histocompatibility complex class I presentation of exogenous soluble tumor antigen fused to the B-fragment of Shiga toxin

Targeting exogenous antigen into the MHC class I-restricted presentation pathway is a prerequisite for the induction of cytotoxic T lymphocytes (CTL) which have been shown to represent an important component of the protective and therapeutic immune response to viral infections and tumors. In this study, we produced recombinant proteins composed of the receptor-binding non-toxic B-fragment of bacterial Shiga toxin derived from Shigella dysenteriae associated with an epitope from a model tumor antigen, Mage 1. We show that Shiga B-Mage 1 fusion proteins carrying an active or inactive endoplasmic reticulum retrieval signal (the C-terminal peptides KDEL or KDELGL, respectively) could be presented by peripheral blood mononuclear cells in an MHC class I-restricted manner to Mage 1-specific CTL. After pulsing B lymphoblastoid cells or dendritic cells with Shiga B-Mage 1 fusion protein, activation of the MHC class I-restricted Mage 1-specific CTL was also demonstrated. In further analysis, we showed that treatment with brefeldin A or paraformaldehyde fixation of Epstein-Barr virus-transformed B cells prevented the presentation of the Mage 1 T cell epitope, which excluded extracellular processing of the antigen. Immunofluorescence analysis also revealed that the Shiga B-Mage 1 fusion protein was largely excluded from Lamp-2-positive lysosomal structures. Therefore, the ability of Shiga toxin B-fragment to target dendritic cells and B cells and to direct antigen into the exogenous class I-restricted pathway makes it an attractive non-living and non-toxic vaccine vector.     

Liquid-phase sintering of TiN-enriched T15-grade high-speed steels and their mechanical properties

The present investigation is an attempt to develop composites based on high-speed steel through liquid-phase sintering route using a powder metallurgical technique. Water-atomised annealed T15-grade HSS powder, lubricant and various mass percents of TiN (0–8%) were blended and axially compacted into green pellets at 850 MPa at room temperature. During sintering studies carried out in vacuum (10^?2 torr), optimum temperature for full densification was determined for each composition. Only full dense sintered samples (density ≥98% theoretical) were selected for further heat treatment and the evaluation of mechanical properties. Mechanical properties like hardness, transverse rupture strength and hot compressive yield strength were evaluated. Both qualitative and quantitative metallographic studies were carried out and chemical analysis of various phases in sintered as well as heat-treated composites were determined using SEM-EDX. The results confirm that fully dense composites containing up to 2% TiN exhibit equivalent mechanical properties, although some differences in service behaviour e.g. wear resistance are to be expected.     

Design of an analytic-hierarchy-process-based expert system for non-traditional machining process selection

The selection of a non-traditional machining (NTM) process is often observed to be a multi-criteria decision-making problem with conflicting and diverse objectives. This paper presents a systematic methodology for selecting the best or optimal non-traditional machining process under constrained material and machining conditions. The paper also includes the design of an analytic-hierarchy-process-based expert system with a graphical user interface to ease the decision-making process. The developed expert system relies on the priority values for different criteria and sub-criteria, as related to a specific non-traditional machining process selection problem. It also depends on the logic table to discover the non-traditional machining processes that lie in the acceptability zone, and then selects the optimal process having the highest acceptability index value. The proposed expert system can automate the selection of a non-traditional machining process and provide artificial intelligence in the multi-criteria decision-making process.     

Colloid cyst xanthogranuloma of the third ventricle--a case report

Diagnosis and treatment of malignant pericardial effusion are difficult in clinical practice. This paper reports the feasibility and reliability of percutanous trans-catheter intervention for the diagnosis and treatment of malignant pericardial effusion. Under echocardiagraphic guidence, pericardial puncture was performed and a heamostasis sheath was placed in situ by Seldinger technique. Through the sheath multiple biopsies of the pericardium were taken for pathological examination. A pigtail catheter was inserted to drain off the effusion. According to pathological report suitable anti-cancer drugs were instilled into the pericardial cavity through indwelling catheter for 3-5 days. The catheter was withdrawn when fluid did not re-accumulate. Diagnosis was made in over 96.0% of the cases. Upon follow-up for 3-6 months, complete remission was seen in 96.0% of the treated patients. No significant complication was found in all patients. Percutaneous trans-catheter intervention is a useful approach for the diagnosis and treatment of malignant pericardial effusion.     

Sorption kinetic studies of water vapour on activated carbon beds

Experimental measurements of the adsorption kinetics of water in activated carbon beds at different values of relative humidity have been made. The development of a simple theoretical model based on inter- and intra-particle mass transfer taking into account the thermal effects of sorption of water in activated carbon beds is described. The comparison of the model results with the experimental data is also presented. It is concluded that a single value of the estimated mass transfer coefficient can be used to reasonably predict the adsorption behaviour of water in activated carbon beds.     

Analysis of a thrust bearing with a viscoelastic lubricant

The characteristics of a thrust bearing with a viscoelastic lubricant have been analysed. The elasticity of the lubricant, the volume rate of flow of lubricant and the ratio of the inner and outer radii of the bearing are characterized by the parameters α, β and σ. The effects of these parameters on the pressure distribution and the load-bearing capacity have been studied.     

Recent Developments in Multiphase Metallic Materials

This paper briefly reviews some recent developments in multiphase metallic materials with a specific emphasis on how fundamental metallurgical understanding has guided the development of materials with tailored micro-structures and useful mechanical properties.