Resonant spin-dependent electron coupling in a III-V/II-VI heterovalent double quantum well

We report on design, fabrication, and magnetooptical studies of a III-V/II-VI hybrid structure containing a GaAs/AlGaAs/ZnSe/ZnCdMnSe double quantum well (QW). The structure design allows one to tune the QW levels into the resonance, thus facilitating penetration of the electron wave function from the diluted magnetic semiconductor ZnCdMnSe QW into the nonmagnetic GaAs QW and vice versa. Magneto-photoluminescence studies demonstrate level anticrossing and strong intermixing resulting in a drastic renormalization of the electron effective g factor, in perfect agreement with the energy level calculations.Comment: 4 pages, 5 Postscript figures, uses revtex

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

Purpose: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. Materials and methods: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. Results: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). Conclusions: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.Peer-reviewedPublisher Version1721

Widespread FRA1-Dependent Control of Mesenchymal Transdifferentiation Programs in Colorectal Cancer Cells

Tumor invasion and metastasis involves complex remodeling of gene expression programs governing epithelial homeostasis. Mutational activation of the RAS-ERK is a frequent occurrence in many cancers and has been shown to drive overexpression of the AP-1 family transcription factor FRA1, a potent regulator of migration and invasion in a variety of tumor cell types. However, the nature of FRA1 transcriptional targets and the molecular pathways through which they promote tumor progression remain poorly understood. We found that FRA1 was strongly expressed in tumor cells at the invasive front of human colorectal cancers (CRCs), and that its depletion suppressed mesenchymal-like features in CRC cells in vitro. Genome-wide analysis of FRA1 chromatin occupancy and transcriptional regulation identified epithelial-mesenchymal transition (EMT)-related genes as a major class of direct FRA1 targets in CRC cells. Expression of the pro-mesenchymal subset of these genes predicted adverse outcomes in CRC patients, and involved FRA-1-dependent regulation and cooperation with TGFβ signaling pathway. Our findings reveal an unexpectedly widespread and direct role for FRA1 in control of epithelial-mesenchymal plasticity in CRC cells, and suggest that FRA1 plays an important role in mediating cross talk between oncogenic RAS-ERK and TGFβ signaling networks during tumor progression.This work was supported by project grants 1026228 and 1044168 (to A.S.D.) and Senior Research Fellowships (to R.D.H., R.B.P. and J.M.M.) from the National Health and Medical Research Council of Australia

Novel monoclonal antibodies detect Smad-Interacting Protein 1 (SIP1) in the cytoplasm of human cells from multiple tumor tissue arrays

Cataloged from PDF version of article.Smad-interacting protein 1 (SIP1, also known as ZEB2) represses the transcription of E-cadherin and mediates epithelial-mesenchymal transition in development and tumor metastasis. Due to the lack of human SIP1-specific antibodies, its expression in human tumor tissues has not been studied in detail by immunohistochemistry. Hence, we generated two anti-SIP1 monoclonal antibodies, clones 1C6 and 6E5, with IgG1 and IgG2a isotypes, respectively. The specificity of these antibodies was shown by Western blotting studies using siRNA mediated downregulation of SIP1 and ZEB1 in a human osteosarcoma cell line. In the same context, we also compared them with 5 commercially available SIP1 antibodies. Antibody specificity was further verified in an inducible cell line system by immunofluorescence. By using both antibodies, we evaluated the tissue expression of SIP1 in paraffin-embedded tissue microarrays consisting of 22 normal and 101 tumoral tissues of kidney, colon, stomach, lung, esophagus, uterus, rectum, breast and liver. Interestingly, SIP1 predominantly displayed a cytoplasmic expression, while the nuclear localization of SIP1 was observed in only 6 cases. Strong expression of SIP1 was found in distal tubules of kidney, glandular epithelial cells of stomach and hepatocytes, implicating a co-expression of SIP1 and E-cadherin. Squamous epithelium of the esophagus and surface epithelium of colon and rectum were stained with moderate to weak intensity. Normal uterus, breast and lung tissues remained completely negative. By comparison with their normal tissues, we observed SIP1 overexpression in cancers of the kidney, breast, lung and uterus. However, SIP1 expression was found to be downregulated in tumors from colon, rectum, esophagus, liver and stomach tissues. Finally we did nuclear/cytoplasmic fractionation in 3 carcinoma cell lines and detected SIP1 in both fractions, nucleus being the dominant one. To our best knowledge, this is the first comprehensive immunohistochemical study of the expression of SIP1 in a series of human cancers. Our finding that SIP1 is not exclusively localized to nucleus suggests that the subcellular localization of SIP1 is regulated in normal and tumor tissues. These novel monoclonal antibodies may help elucidate the role of SIP1 in tumor development. © 2010 Elsevier Inc

Experimental study of subcooled water spray cooling using flow symmetric micro-structured surfaces

Spray impingement cooling has been shown to be a leading candidate for future high heat flux cooling applications. In general, spray cooling curves consist of three heat flux regimes; single-phase, two-phase and critical heat flux (CHF). CHF is considered the design limit for almost all two-phase cooling applications, as a rapid increase in temperature and decrease in heat flux occurs beyond this point. Recent studies have shown that the addition of micro-structures on the impingement surface can enhance heat transfer relative to a smooth surface. In the present study, spray cooling curves are obtained for two micro-structured surfaces and are compared to smooth surface results. Micro-structured surfaces consisted of bio-inspired fractal-like geometries, denoted as grooves and fins, extending in a radial direction from the center to the periphery of a 37.8 mm circular disc. Depending on the location on the surface, dimensions of groove widths and heights varied from 100 to 500 μm, and 30 to 60 μm, respectively. Fin width and height dimension remained constant throughout the surface at 127 and 60 μm, respectively. Heat flux and wall temperature at the impingement surface were calculated from temperature data measured at multiple locations below the impingement surface. Results are presented as heat flux, q" , versus the wall-to-spray temperature difference, ΔT[subscript w], at each of 5 volume flux, Q", conditions ranging from 0.54 to 2.04 x 10⁻³ m³/m²s. Convection coefficients, h[subscript cv], and spray efficiencies, η, are also presented for each case as a function of q" and ΔT[subscript w] , respectively. Results of the study indicate that at low and high volume fluxes, an improvement in heat transfer occurs in the single-phase regime for the fin geometry. Enhancement in the single-phase regime did not occur at the intermediate volume flux condition of 1.37 x 10⁻³ m³/m²s. At all volume flux states tested, significant enhancements, as high as 50% in some cases, were observed in the two-phase regime for the fin structure, whereas the groove structure performed identically to the flat surface in the single-phase regime and exhibited a large degradation in the two-phase and critical heat flux regimes (~50%). Critical heat flux for the fin surface compared to the flat surface was slightly lower at low volume flux conditions, equivalent at the intermediate volume flux, and slightly greater at high volume flux conditions. Further investigations into the underlying mechanisms responsible for these results are needed

FISCAL STIMULATION OF SPATIAL DEVELOPMENT: THE EU COUNTRIES’ CASES

The objective of this article is to form the basis for strengthening the fiscal stimulus spatial development of regional economic systems in the context of decentralization. The methods of research: dialectical, synthesis, analysis, generalizations and monographic, abstraction and generalizations. Results. The authors consider the «fiscal space» as a certain economic spatial formation, formed by elements of the regional economic system, which are involved in the construction of budget components and management of financial flows. The positive impact of the fiscal policy’s implementation in the context of decentralization is highlighted, as well as a certain imbalance of certain areas that provoke the search for ways of fiscal policy objectives intra-regional coordination. Summarizing the experience of European countries on fiscal stimulation of the development of regional economic systems, the following trends are highlighted: first, the main regulatory instruments are tax and budgetary policies, the level of their development and independence in the regions of countries; secondly, regional fiscal policy is always subordinated to the national economic development strategy; thirdly, taxes are becoming a tool for both stimulating and restraining the regions’ development. The article proposes the ways to smooth out negative challenges and the task of regional development’s fiscal stimulation is defined. The experience of European countries allows us to explore the prospects for developing tools for fiscal stimulus to ensure the sustainability and modernization of the regional space. Conclusions. The experience of European countries in the implementation of fiscal policy in the context of decentralization and the functioning of local self-government is studied. Despite the binding nature and dominance of European norms in fiscal policy, each country has formed its own strategic goals in economic development. This allowed preserving the national identity of individual territories, the specificity of the cultural value’s impact on the fiscal stimulation of regional economic systems. The authors come to the conclusion that the adaptation of the best practices in European countries in the Ukrainian economy’s conditions requires their reformatting under the goals and strategies of national economic policy. Directions of implementation of EU countries’ experience in fiscal stimulus of regional space in Ukraine are identified in the article

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido

Epigenetic regulation of S100 protein expression

S100 proteins are small, calcium-binding proteins whose genes are localized in a cluster on human chromosome 1. Through their ability to interact with various protein partners in a calcium-dependent manner, the S100 proteins exert their influence on many vital cellular processes such as cell cycle, cytoskeleton activity and cell motility, differentiation, etc. The characteristic feature of S100 proteins is their cell-specific expression, which is frequently up- or downregulated in various pathological states, including cancer. Changes in S100 protein expression are usually characteristic for a given type of cancer and are therefore often considered as markers of a malignant state. Recent results indicate that changes in S100 protein expression may depend on the extent of DNA methylation in the S100 gene regulatory regions. The range of epigenetic changes occurring within the S100 gene cluster has not been defined. This article reviews published data on the involvement of epigenetic factors in the control of S100 protein expression in development and cancer

Continuing the conversation about public health ethics: education for public health professionals in Europe

An important related question is why we should teach public health ethics. Fundamentally, we must teach public health ethics because ethical practice creates and maintains public trust and public health cannot function without public trust. To serve the public—whether through controlling an outbreak of an infectious disease, preparing for or responding to public health emergencies, or reducing the impact of non-communicable diseases—communities and individuals must trust our decisions and actions. This trust grows in large part from past successes, transparent and participatory decision making, and ethical management of the inevitable moral tensions that arise in our work.S