PPARs and Tumor Microenvironment: The Emerging Roles of the Metabolic Master Regulators in Tumor Stromal-Epithelial Crosstalk and Carcinogenesis.

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. Their roles in malignancy are also increasingly recognized. With the growing interest in crosstalk between tumor stroma and epithelium, this review aims to highlight the current knowledge on the implications of PPARs in the tumor microenvironment. PPARγ plays a crucial role in the metabolic reprogramming of cancer-associated fibroblasts and adipocytes, coercing the two stromal cells to become substrate donors for cancer growth. Fibroblast PPARβ/δ can modify the risk of tumor initiation and cancer susceptibility. In endothelial cells, PPARβ/δ and PPARα are pro- and anti-angiogenic, respectively. Although the angiogenic role of PPARγ remains ambiguous, it is a crucial regulator in autocrine and paracrine signaling of cancer-associated fibroblasts and tumor-associated macrophages/immune cells. Of note, angiopoietin-like 4 (ANGPTL4), a secretory protein encoded by a target gene of PPARs, triggers critical oncogenic processes such as inflammatory signaling, extracellular matrix derangement, anoikis resistance and metastasis, making it a potential drug target for cancer treatment. To conclude, PPARs in the tumor microenvironment exhibit oncogenic activities which are highly controversial and dependent on many factors such as stromal cell types, cancer types, and oncogenesis stages. Thus, the success of PPAR-based anticancer treatment potentially relies on innovative strategies to modulate PPAR activity in a cell type-specific manner

The Role of Translation Initiation Regulation in Haematopoiesis

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control

Entanglement preparation using symmetric multiports

We investigate the entanglement produced by a multi-path interferometer that is composed of two symmetric multiports, with phase shifts applied to the output of the first multiport. Particular attention is paid to the case when we have a single photon entering the interferometer. For this situation we derive a simple condition that characterize the types of entanglement that one can generate. We then show how one can use the results from the single photon case to determine what kinds of multi-photon entangled states one can prepare using the interferometer.Comment: 6 pages, 2 figures, accepted for publication in European Journal of Physics

Entanglement preparation using symmetric multiports

We investigate the entanglement produced by a multi-path interferometer that is composed of two symmetric multiports, with phase shifts applied to the output of the first multiport. Particular attention is paid to the case when we have a single photon entering the interferometer. For this situation we derive a simple condition that characterize the types of entanglement that one can generate. We then show how one can use the results from the single photon case to determine what kinds of multi-photon entangled states one can prepare using the interferometer.Comment: 6 pages, 2 figures, accepted for publication in European Journal of Physics

Surface preparation of powder metallurgical tool steels by means of wire electrical discharge machining

The surface of two types of powder metallurgical (PM) tool steels (i.e., with and without nitrogen) was prepared using wire electrical discharge machining (WEDM). From each grade of tool steel, seven surfaces corresponding to one to seven passes of WEDM were prepared. The WEDM process was carried out using a brass wire as electrode and deionized water as dielectric. After eachWEDM pass the surface of the tool steels was thoroughly examined. Surface residual stresses were measured by the X-ray diffraction (XRD) technique. The measured stresses were found to be of tensile nature. The surface roughness of the WEDM specimens was measured using interference microscopy. The surface roughness as well as the residual stress measurements indicated an insignificant improvement of these parameters after four passes of WEDM. In addition, the formed recast layer was characterized by means of scanning electron microscopy (SEM), XRD, and X-ray photoelectron spectroscopy (XPS). The characterization investigation clearly shows diffusion of copper and zinc from the wire electrode into the work material, even after the final WEDM step. Finally, the importance of eliminating excessive WEDM steps is thoroughly discussed

Precipitate Redistribution During Creep of Alloy 617

Nickel-based superalloys are being considered for applications within advanced nuclear power generation systems due to their high temperature strength and corrosion resistance. Alloy 617, a candidate for use in heat exchangers, derives its strength from both solid solution strengthening and the precipitation of carbide particles. However, during creep, carbides that are supposed to retard grain boundary motion are found to dissolve and re-precipitate on boundaries in tension. To quantify the redistribution, we have used electron backscatter diffraction and energy dispersive spectroscopy to analyze the microstructure of 617 after creep testing at 900 and 1000°C. The data were analyzed with respect to location of the carbides (e.g., intergranular vs. intragranular), grain boundary character, and precipitate type (i.e., Cr-rich or Mo-rich). We find that grain boundary character is the most important factor in carbide distribution; some evidence of preferential distribution to boundaries in tension is also observed at higher applied stresses. Finally, the results suggest that the observed redistribution is due to the migration of carbides to the boundaries and not the migration of boundaries to the precipitates

Tau Polarization Asymmetry in B→Xsτ+τ−B\to X_s\tau^+\tau^-

Rare $B$ decays provide an opportunity to probe for new physics beyond the Standard Model. In this paper, we propose to measure the tau polarization in the inclusive decay $B\to X_s\tau^+\tau^-$ and discuss how it can be used, in conjunction with other observables, to completely determine the parameters of the flavor-changing low-energy effective Hamiltonian. Both the Standard Model and several new physics scenarios are examined. This process has a large enough branching fraction, $\sim {\rm few}\times 10^{-7}$, such that sufficient statistics will be provided by the B-Factories currently under construction.Comment: 11 pages, LaTex file with psfig. Figures included via uufiles. Lengthened version. Includes new calculation of Monte Carlo fit to Wilson coefficient

Measuring children’s involvement as an indicator of curriculum effectiveness : a curriculum evaluation of a selected child study centre in Singapore

This paper presents one aspect of a research project evaluating a curriculum model of a selected child study centre in Singapore. An issue of worldwide interest and concern is the ‘quality of learning’ debate as it relates to early childhood centres. In Singapore, the government is focusing on expansion in child care settings and increases in the amount of funded training. One of the issues surrounding prior-to-school education raises the question of how one measures the quality of teaching and learning, to describe the value of using, funding and promoting early education. The research reported in this study used a quasi experimental research paradigm to assess one aspect of the quality of a curriculum programme in a child study centre in Singapore. Children aged between 18 months and 6 years (N = 81) participated in the research. Using the observation scale of Laevers’ Child Involvement Scale, the active involvement of children in learning experiences was measured. The findings are presented and discussed