Discourse and identity in a corpus of lesbian erotica

This article uses corpus linguistic methodologies to explore representations of lesbian desires and identities in a corpus of lesbian erotica from the 1980s and 1990s. We provide a critical examination of the ways in which “lesbian gender,” power, and desire are represented, (re-)produced, and enacted, often in ways that challenge hegemonic discourses of gender and sexuality. By examining word frequencies and collocations, we critically analyze some of the themes, processes, and patterns of representation in the texts. Although rooted in linguistics, we hope this article provides an accessible, interdisciplinary, and timely contribution toward developing understandings of discursive practices surrounding gender and sexuality

Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor β Superfamily Type 1 Receptors.

The transforming growth factor β (TGFβ) superfamily includes TGFβ, activins, inhibins, and bone morphogenetic proteins (BMPs). These extracellular ligands have essential roles in normal tissue homeostasis by coordinately regulating cell proliferation, differentiation, and migration. Aberrant signaling of superfamily members, however, is associated with fibrosis as well as tumorigenesis, cancer progression, metastasis, and drug-resistance mechanisms in a variety of cancer subtypes. Given their involvement in human disease, the identification of novel selective inhibitors of TGFβ superfamily receptors is an attractive therapeutic approach. Seven mammalian type 1 receptors have been identified that have context-specific roles depending on the ligand and the complex formation with the type 2 receptor. Here, we characterize the biologic effects of two transforming growth factor β receptor 1 (TGFBR1) kinase inhibitors designed to target TGFβ signaling. AZ12601011 [2-(2-pyridinyl)-4-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine]; structure previously undisclosed] and AZ12799734 [4-({4-[(2,6-dimethyl-3-pyridinyl)oxy]-2-pyridinyl}amino)benzenesulfonamide] (IC50 = 18 and 47 nM, respectively) were more effective inhibitors of TGFβ-induced reporter activity than SB-431542 [4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide] (IC50 = 84 nM) and LY2157299 [4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide monohydrate]] (galunisertib) (IC50 = 380 nM). AZ12601011 inhibited phosphorylation of SMAD2 via the type 1 receptors activin A receptor type 1B (ALK4), TGFBR1, and activin A receptor type 1C (ALK7). AZ12799734, however, is a pan TGF/BMP inhibitor, inhibiting receptor-mediated phosphorylation of SMAD1 by activin A receptor type 1L, bone morphogenetic protein receptor type 1A, and bone morphogenetic protein receptor type 1B and phosphorylation of SMAD2 by ALK4, TGFBR1, and ALK7. AZ12601011 was highly effective at inhibiting basal and TGFβ-induced migration of HaCaT keratinocytes and, furthermore, inhibited tumor growth and metastasis to the lungs in a 4T1 syngeneic orthotopic mammary tumor model. These inhibitors provide new reagents for investigating in vitro and in vivo pathogenic processes and the contribution of TGFβ- and BMP-regulated signaling pathways to disease states

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.</p

The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

Theories of the Firm and their Value Creation Assumptions

Since Coase’s (1937) seminal paper on ‘The Nature of the Firm’, strategy scholars are invested in developing so-called ‘theories of the firm’ (ToFs). These are theories that should answer four questions on the nature of firms: Why do firms exist? Why are their boundaries as they are? Why are they organized the way they are? and Why are they so heterogeneous? In answering these questions, at least twenty ToFs have been put forward in the last decades. These include economics-based ToFs such as principal-agent theory and transaction-cost economics; organization theory-based ToFs such as behavioral theory and bureaucratic theory; and strategy-based ToFs such as the value-chain model and stakeholder theory. Assuming that all ToFs attempt to answer the four questions above, the question arises why we would need so many ToFs. Do we really need so many? And, if so, why? The extant literature provides a partial answer to this question by looking at complementarities between ToFs. Along that line, scholars have suggested to combine various ToFs (e.g., Coff, 1999; Foss & Foss, 2005; Pitelis, 2007). However, as these suggestions typically concern the combination of two or of three ToFs, they do not account for the fact that we have at least twenty now. Also more comprehensive reviews (e.g., Conner, 1991; Foss, 1993; Madhok, 2002) do not explain the multitude of ToFs in our literature. To find an answer to this question, this paper provides a two-step comparison of ToFs. The first step is a bird’s eye view comparison of eighteen well-known ToFs along some apparent differences. This step reveals differences between some ToFs, but it also leaves a group of ToFs that are apparently similar. In the second step we further compare this group of ToFs on their more implicit assumptions. Based on this two-step comparison, we conclude that we do indeed need a variety of ToF. The reason is that the various ToFs have different assumptions on how firms create value and from which sources this value is derived. Since firms in practice also differ in the way they create value, our conclusion is that we need more than one ToF to explain this variety. The implication is that scholars engaged in the ToF debate may want to put firm value creation center stage. This, we shall argue, requires adding a fifth question to the ToF that precedes the other four questions: what value does a firm create

Anisotropic Colossal Magnetoresistance Effects in Fe_{1-x}Cu_xCr_2S_4

A detailed study of the electronic transport and magnetic properties of Fe$_{1-x}$Cu$_x$Cr$_2$S$_4$ ($x \leq 0.5$) on single crystals is presented. The resistivity is investigated for $2 \leq T \leq 300$ K in magnetic fields up to 14 Tesla and under hydrostatic pressure up to 16 kbar. In addition magnetization and ferromagnetic resonance (FMR) measurements were performed. FMR and magnetization data reveal a pronounced magnetic anisotropy, which develops below the Curie temperature, $T_{\mathrm{C}}$, and increases strongly towards lower temperatures. Increasing the Cu concentration reduces this effect. At temperatures below 35 K the magnetoresistance, $MR = \frac{\rho(0) - \rho(H)}{\rho(0)}$, exhibits a strong dependence on the direction of the magnetic field, probably due to an enhanced anisotropy. Applying the field along the hard axis leads to a change of sign and a strong increase of the absolute value of the magnetoresistance. On the other hand the magnetoresistance remains positive down to lower temperatures, exhibiting a smeared out maximum with the magnetic field applied along the easy axis. The results are discussed in the ionic picture using a triple-exchange model for electron hopping as well as a half-metal utilizing a band picture.Comment: some typos correcte

Fatal attractions? Correlations of CXCL12–CXCR4–CXCR7 expression with disease progression in melanoma and Kaposi sarcoma

No abstract available

Targeting BRAF-mutant tumours with TGFBR1 inhibitors

No abstract available

“Making voices heard…”: Index on Censorship as Advocacy Journalism

The magazine Index on Censorship has sought, since its launch in 1972, to provide a space where censorship and abuses against freedom of expression have been identified, highlighted and challenged. Originally set up by a collection of writers and intellectuals who were concerned at the levels of state censorship and repression of artists in and under the influence of the Soviet Union and elsewhere, ‘Index’ has provided those championing the values of freedom of expression with a platform for highlighting human rights abuses, curtailment of civil liberties and formal and informal censorship globally. Charting its inception and development between 1971 and 1974, the paper is the first to situate the journal within the specific academic literature on activist media (Janowitz, 1975; Waisbord, 2009; Fisher, 2016). In doing so the paper advances an argument which draws on the drivers and motivations behind the publication’s launch to signal the development of a particular justification or ‘advocacy’ of a left-libertarian civic model of freedom of speech

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator