A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

Mechanisms of internalization and recycling of the chemokine receptor, CCR5

CCR5 is a G protein-coupled receptor that binds several natural chemokines but it is also a coreceptor for the entry of M tropic strains of HIV-1 into cells. Levels of CCR5 on the cell surface are important for the rate of HIV-1 infection and are determined by a number of factors including the rates of CCR5 internalization and recycling. Here we investigated the involvement of the actin cytoskeleton in the control of ligand-induced internalization and recycling of CCR5. Cytochalasin D, an actin depolymerizing agent, inhibited chemokine-induced internalization of CCR5 and recycling of the receptor in stably transfected CHO cells and in the monocytic cell line, THP-1. CCR5 internalization and recycling were inhibited by Toxin B and C-3 exoenzyme treatment in CHO and THP-1 cells, confirming activation of members of the RhoGTPase family by CCR5. The specific Rho kinase inhibitor Y27632, however, had no effect on CCR5 internalization or recycling. Ligand-induced activation of CCR5 leads to Rho kinase-dependent formation of focal adhesion complexes. These data indicate that CCR5 internalization and recycling are regulated by actin polymerization and activation of small G proteins in a Rho-dependent manner.

Dual role of the beta(2)-adrenergic receptor C terminus for the binding of beta-arrestin and receptor internalization

Homologous desensitization of beta(2)-adrenergic and other G-protein-coupled receptors is a two-step process. After phosphorylation of agonist-occupied receptors by G-protein-coupled receptor kinases, they bind beta-arrestins, which triggers desensitization and internalization of the receptors. Because it is not known which regions of the receptor are recognized by beta-arrestins, we have investigated beta-arrestin interaction and internalization of a set of mutants of the human beta(2)-adrenergic receptor. Mutation of the four serine/threonine residues between residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2 interaction as revealed by fluorescence resonance energy transfer (FRET), translocation of beta-arrestin2 to the plasma membrane, and receptor internalization. Mutation of all seven serine/threonine residues distal to residue 381 did not affect agonist-induced receptor internalization and beta-arrestin2 translocation. A beta(2)-adrenergic receptor truncated distal to residue 381 interacted normally with beta-arrestin2, whereas its ability to internalize in an agonist-dependent manner was compromised. A similar impairment of internalization was observed when only the last eight residues of the C terminus were deleted. Our experiments show that the C terminus distal to residue 381 does not affect the initial interaction between receptor and beta-arrestin, but its last eight amino acids facilitate receptor internalization in concert with beta-arrestin2.

Characterisation of soils containing naturally occurring radioactive material (NORM) using in situ and rapid laboratory techniques. Case study: South Terras, Cornwall

In situ analysis has become increasingly important for contaminated land investigation and remediation. At present, portable techniques are used mainly as scanning tools to assess the spread and magnitude of the contamination, and are an adjunct to conventional laboratory analyses. A site in Cornwall, containing naturally occurring radioactive material (NORM), provided an opportunity for Reading University PhD student Anna Kutner to compare analytical data collected in situ with data generated by laboratory-based methods. The preliminary results in this paper extend the author‟s poster presentation at last September‟s GeoSpec2010 conference held in Lancaster.

'Quasi'-norm of an arithmetical convolution operator and the order of the Riemann zeta function

In this paper we study Dirichlet convolution with a given arithmetical function f as a linear mapping 'f that sends a sequence (an) to (bn) where bn = Pdjn f(d)an=d. We investigate when this is a bounded operator on l2 and ¯nd the operator norm. Of particular interest is the case f(n) = n¡® for its connection to the Riemann zeta function on the line 1, 'f is bounded with k'f k = ³(®). For the unbounded case, we show that 'f : M2 ! M2 where M2 is the subset of l2 of multiplicative sequences, for many f 2 M2. Consequently, we study the `quasi'-norm sup kak = T a 2M2 k'fak kak for large T, which measures the `size' of 'f on M2. For the f(n) = n¡® case, we show this quasi-norm has a striking resemblance to the conjectured maximal order of j³(® + iT )j for ® > 12 .

A multidimensional comparison of discourse organization in English and Chinese university students' argumentative writing

Three methodological limitations in English-Chinese contrastive rhetoric research have been identified in previous research, namely: the failure to control for the quality of L1 data; an inference approach to interpreting the relationship between L1 and L2 writing; and a focus on national cultural factors in interpreting rhetorical differences. Addressing these limitations, the current study examined the presence or absence and placement of thesis statement and topic sentences in four sets of argumentative texts produced by three groups of university students. We found that Chinese students tended to favour a direct/deductive approach in their English and Chinese writing, while native English writers typically adopted an indirect/inductive approach. This study argues for a dynamic and ecological interpretation of rhetorical practices in different languages and cultures.

Platelet endothelial cell adhesion molecule-1 inhibits platelet response to thrombin and von Willebrand factor by regulating the internalization of glycoprotein Ib via AKT/glycogen synthase kinase-3/dynamin and integrin αIIbβ3

OBJECTIVE: Platelet endothelial cell adhesion molecule-1 (PECAM-1) regulates platelet response to multiple agonists. How this immunoreceptor tyrosine-based inhibitory motif-containing receptor inhibits G protein-coupled receptor-mediated thrombin-induced activation of platelets is unknown. APPROACH AND RESULTS: Here, we show that the activation of PECAM-1 inhibits fibrinogen binding to integrin αIIbβ3 and P-selectin surface expression in response to thrombin (0.1-3 U/mL) but not thrombin receptor-activating peptides SFLLRN (3×10(-7)-1×10(-5) mol/L) and GYPGQV (3×10(-6)-1×10(-4) mol/L). We hypothesized a role for PECAM-1 in reducing the tethering of thrombin to glycoprotein Ibα (GPIbα) on the platelet surface. We show that PECAM-1 signaling regulates the binding of fluorescein isothiocyanate-labeled thrombin to the platelet surface and reduces the levels of cell surface GPIbα by promoting its internalization, while concomitantly reducing the binding of platelets to von Willebrand factor under flow in vitro. PECAM-1-mediated internalization of GPIbα was reduced in the presence of both EGTA and cytochalasin D or latrunculin, but not either individually, and was reduced in mice in which tyrosines 747 and 759 of the cytoplasmic tail of β3 integrin were mutated to phenylalanine. Furthermore, PECAM-1 cross-linking led to a significant reduction in the phosphorylation of glycogen synthase kinase-3β Ser(9), but interestingly an increase in glycogen synthase kinase-3α pSer(21). PECAM-1-mediated internalization of GPIbα was reduced by inhibitors of dynamin (Dynasore) and glycogen synthase kinase-3 (CHIR99021), an effect that was enhanced in the presence of EGTA. CONCLUSIONS: PECAM-1 mediates internalization of GPIbα in platelets through dual AKT/protein kinase B/glycogen synthase kinase-3/dynamin-dependent and αIIbβ3-dependent mechanisms. These findings expand our understanding of how PECAM-1 regulates nonimmunoreceptor signaling pathways and helps to explains how PECAM-1 regulates thrombosis.

e-Leadership through strategic alignment: an empirical study of small and medium sized enterprises in the digital age

Small and medium sized enterprises (SMEs) play an important role in the European economy. A critical challenge faced by SME leaders, as a consequence of the continuing digital technology revolution, is how to optimally align business strategy with digital technology to fully leverage the potential offered by these technologies in pursuit of longevity and growth. There is a paucity of empirical research examining how e-leadership in SMEs drives successful alignment between business strategy and digital technology fostering longevity and growth. To address this gap, in this paper we develop an empirically derived e-leadership model. Initially we develop a theoretical model of e-leadership drawing on strategic alignment theory. This provides a theoretical foundation on how SMEs can harness digital technology in support of their business strategy enabling sustainable growth. An in-depth empirical study was undertaken interviewing 42 successful European SME leaders to validate, advance and substantiate our theoretically driven model. The outcome of the two stage process – inductive development of a theoretically driven e-leadership model and deductive advancement to develop a complete model through in-depth interviews with successful European SME leaders – is an e-leadership model with specific constructs fostering effective strategic alignment. The resulting diagnostic model enables SME decision makers to exercise effective e-leadership by creating productive alignment between business strategy and digital technology improving longevity and growth prospects.

Comparing performance of instrumental drift correction by linear and quadratic adjusting in inductive electromagnetic data

Electromagnetic induction (EMI) method results are shown for vertical magnetic dipole (VMD) configuration by using the EM38 equipment. Performance in the location of metallic pipes and electrical cables is compared as a function of instrumental drift correction by linear and quadratic adjusting under controlled conditions. Metallic pipes and electrical cables are buried at the IAG/USP shallow geophysical test site in Sao Paulo City. Brazil. Results show that apparent electrical conductivity and magnetic susceptibility data were affected by ambient temperature variation. In order to obtain better contrast between background and metallic targets it was necessary to correct the drift. This correction was accomplished by using linear and quadratic relation between conductivity/susceptibility and temperature intending comparative studies. The correction of temperature drift by using a quadratic relation was effective, showing that all metallic targets were located as well deeper targets were also improved. (C) 2010 Elsevier B.V. All rights reserved.

International conference site selection criteria : And a case study of Stockholm as an international conference city

The purpose of this thesis is to identify the destination site selection criteria for internationalconferences from the perspectives of the three main players of the conference industry,conference buyers (organizers and delegates) and suppliers. Additionally, the researchidentifies the strengths and weaknesses of the congress cities of Stockholm and Vienna.Through a comparison with Vienna, the top city for hosting international conferences, a roadmap for Stockholm has been designed, to strengthen its congress tourism opportunities, thus,obtaining a higher status as an international congress city. This qualitative research hascombined both primary and secondary data methods, through semi-standardized expertinterviews and secondary studies respectively, to fulfil the study’s aim. The data have beenanalysed by applying the techniques of qualitative content analysis; the secondary dataadopting an inductive approach according to Mayring (2003) while the expert interviewsusing a deductive approach according to Meuser & Nagel (2009). The conclusions of thesecondary data have been further compared and contrasted with the outcomes of the primarydata, to propose fresh discoveries, clarifications, and concepts related to the site selectioncriteria for international conferences, and for the congress tourism industry of Stockholm. Theresearch discusses the discoveries of the site selection criteria, the implications of thestrengths and weaknesses of Stockholm in comparison to Vienna, recommendations forStockholm via a road map, and future research areas in detail. The findings andrecommendation, not only provide specific steps and inceptions that Stockholm as aninternational conference city can apply, but also propose findings, which can aid conferencebuyers and suppliers to cooperate, to strengthen their marketing strategies and developsuccessful international conferences and destinations to help achieve a greater competitiveadvantage.

System for Automated Deduction (SAD): Linguistic and Deductive Peculiarities

In this paper a state of the art of a system of automated deduction called SAD is described . An architecture of SAD corresponds well to a modern vision of the Evidence Algorithm programme, initiated by Academician V.Glushkov.