Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.     

Tissue culture surface characteristics influence the expansion of human bone marrow cells

Human cell therapy applications in tissue engineering, such as the ex vivo production of hematopoietic cells for transplantation, have recently entered the clinic. Although considerable effort has been focused on the development of biological processes to generate therapeutic cells, little has been published on the design and manufacture of devices for implementation of these processes in a robust and reproducible fashion at a clinical scale. In this study, the effect of tissue culture surface chemistry and texture was assessed in human bone marrow (BM) mononuclear cell (MNC) and CD34-enriched cell cultures. Growth and differentiation was assessed by total, progenitor (CFU-GM), stromal (CFU-F), and primitive (LTC-IC) cell output. Tissue culture treated (TCT) plastic significantly increased MNC culture output as compared with non-TCT plastic, whereas CD34-enriched cell cultures gave lower output (than MNC cultures) that was unaffected by TCT plastic. Interestingly, the level of MNC culture output was significantly different on four commercial TCT surfaces, with the best performing surface giving output that was 1.6- to 2.8-fold greater than the worst one. The surface giving the highest output was the best at supporting development of a distinct morphological feature in the adherent layer (i.e. cobblestone area) indicative of primitive cells, and X-ray photoelectron spectroscopy (XPS) was used to characterize this surface. For custom injection molding of culture devices, the use of three different resins resulted in MNC culture output that was equivalent to commercial cultureware controls, whereas CD34-enriched cell cultures were highly sensitive to resins containing additives. When the texture of molded parts was roughened by sandblasting of the tool, MNC culture output was significantly reduced and higher spikes of IL-6 and G-CSF production were observed, presumably due to macrophage activation. In conclusion, the manufacture of BM MNC culture devices for clinical applications was optimized by consideration of plastic resin, surface treatment, and texture of the culture substratum. Although CD34-enriched cells were insensitive to surface treatment, they were considerably more sensitive to biocompatibility issues related to resin selection. The development of robust systems for BM MNC expansion will enable clinical trials designed to test the safety and efficacy of cells produced in this novel tissue engineering application.     

The regulation of reactive oxygen species production during programmed cell death

Reactive oxygen species (ROS) are thought to be involved in many forms of programmed cell death. The role of ROS in cell death caused by oxidative glutamate toxicity was studied in an immortalized mouse hippocampal cell line (HT22). The causal relationship between ROS production and glutathione (GSH) levels, gene expression, caspase activity, and cytosolic Ca2+ concentration was examined. An initial 5-10-fold increase in ROS after glutamate addition is temporally correlated with GSH depletion. This early increase is followed by an explosive burst of ROS production to 200-400-fold above control values. The source of this burst is the mitochondrial electron transport chain, while only 5-10% of the maximum ROS production is caused by GSH depletion. Macromolecular synthesis inhibitors as well as Ac-YVAD-cmk, an interleukin 1beta-converting enzyme protease inhibitor, block the late burst of ROS production and protect HT22 cells from glutamate toxicity when added early in the death program. Inhibition of intracellular Ca2+ cycling and the influx of extracellular Ca2+ also blocks maximum ROS production and protects the cells. The conclusion is that GSH depletion is not sufficient to cause the maximal mitochondrial ROS production, and that there is an early requirement for protease activation, changes in gene expression, and a late requirement for Ca2+ mobilization.     

Endometriosis and the neoplastic process

Endometriosis is a frequent disorder that commonly presents with infertility and pelvic pain. Although the precise aetiology of endometriosis is unclear, it is generally considered to involve multiple genetic, environmental, immunological, angiogenic and endocrine processes. Genetic factors have been implicated in endometriosis but the susceptibility genes remain largely unknown. Although endometriosis is a benign disorder, recent studies of endometriosis suggest endometriosis could be viewed as a neoplastic process. Evidence to support this hypothesis includes the increased susceptibility to develop ovarian clear-cell and endometrioid cancers in the presence of endometriosis, and molecular similarities between endometriosis and cancer. In this article we discuss (i) the evidence suggesting that endometriosis might be viewed as a neoplastic process, and (ii) the implications of this hypothesis for elucidating the pathogenesis of endometriosis and developing novel methods of diagnostic classification and individualised treatments.     

Sequencing with limited flexibility

We consider the problem of resequencing a set of prearranged jobs when there is limited resequencing flexibility and sequence-dependent changeover costs. Resequencing flexibility is limited by how far forward or backward a job can shift in the sequence relative to its original position. We show how the problem can be solved using dynamic programming in polynomial time with respect to the number of jobs. We also show how the same solution approach can be extended to problems where sequencing constraints are job specific and to problems where job features, which determine changeover costs, are jointly determined with the job sequence. We provide an integer programming formulation to the resequencing problem whose linear programming relaxation offers a useful lower bound. We also describe a family of decomposition heuristics that are easy to customize to provide desired levels of solution quality and solution time. We document the quality of the lower bound from the linear programming relaxation and the upper bound from the heuristic using numerical results. We also provide numerical results to support managerial insights regarding the value of flexibility. We show that the value of flexibility is of the diminishing kind with most of the benefit realized with relatively limited flexibility. We also show that a balanced allocation of flexibility among forward and backward position shifting is superior to an unbalanced one. More significantly, we show that forward and backward position shifting flexibility are complements with the value of one increasing in the amount of the other. Finally, we apply our solution approach to a real-world case from the automotive industry.     

Civil Engineering Education and Complex Systems

Civil engineering is an interdisciplinary field, and most of the projects designed and built represent very complex systems, both during the construction phase and in the built phase. This research describes how a course in land development that included engineering design elements, lectures that also touched on other related fields, and a field journal assignment at a “green” (sustainable) construction site facilitated students’ understanding of complex systems. Results suggest that this course design facilitates the development of students’ proficiencies in several skill sets, and can increase students’ understanding of the complexity involved in civil engineering projects.     

Grafting of vinyl acetate onto chitosan and biocidal activity of the graft copolymers

The reaction process of polycarbosilane (PCS) fiber cured by cyclohexene vapor has been studied and compared with that of PCS fiber cured by air. The influence of curing temperature on Si? H bond reaction degree and gel content, the structure and composition of PCS were investigated by FTIR, EA, TGA, NMR, and GC‐MS. The results showed that, Si? H bond in the molecular structure of PCS reacted during cyclohexene curing process and the reaction degree increased when the curing temperature increases. Simultaneously, gel content of PCS fiber rapidly increased till PCS fiber became infusible. Si? H radical and Si? CH₂ radicals formed Si? CH₂? Si crosslinking of PCS molecules through the agency of cyclohexene. Some cyclohexyls linked to principal chain of PCS, which was proven by ¹³C‐CPMAS‐NMR, and broke off, and cyclohexane and some monosilane are generated as byproducts when temperature increased. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Texture development in long lengths of NiFe tapes for superconducting coated conductor

A highly oriented cubic texture (full width at half maximum <10°) has been formed in long length NiFe tapes. The X-ray diffraction (XRD), electron back-scattered patterns (EBSP) and optical microscopy (OM) techniques have been used in assessing the surface and volume texture and also the surface morphology of these kilometer long NiFe substrates. This texture was formed under a range of conditions including dynamic annealing in a reduced atmosphere and static annealing in hydrogen and in vacuum. Heat treatment for excessive times in vacuum tends to roughen the surface and should be avoided. Mechanical polishing can induce an additional undesirable texture, but electropolishing gives smooth tapes with good texture.     

Complementary techniques for the characterization of thin film Ti/Nb multilayers

An aberration corrector on the probe-forming lens of a scanning TEM (STEM) equipped with an electron energy-loss spectrometer (EELS) and X-ray energy-dispersive spectrometer (XEDS) has been employed to investigate the compositional variations as a function of length scale in nanoscale Ti/Nb metallic multilayers. The composition profiles of EELS and XEDS were compared with the profiles obtained from the complementary technique of 3D atom probe tomography. At large layer widths (h≥7 nm, where h is the layer width) of Ti and Nb, XEDS composition profiles of Ti/Nb metallic multilayers are in good agreement with the EELS results. However, at reduced layer widths (h≈2 nm), profiles of EELS and atom probe exhibited similar compositional variations, whereas XEDS results have shown a marked difference. This difference in the composition profiling of the layers has been addressed with reference to the effects of beam broadening and the origin of the signals collected in these techniques. The advantage of using EELS over XEDS for these nanoscaled multilayered materials is demonstrated.