927 research outputs found
Theories of the Firm and their Value Creation Assumptions
Since Coaseās (1937) seminal paper on āThe Nature of the Firmā, strategy scholars are invested in developing so-called ātheories of the firmā (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 birdās 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
Edith T. Penrose: Economist of āThe Ordinary Business of Lifeā
When Edith T. Penrose became Fritz Machlupās student in the late-1940s, she found little in mainstream or Austrian economics to guide her as she began her explorations into the growth of the firm. While she acknowledged Kenneth Bouldingās influence on her work, we suspect she drew on a broader tradition that includes, among others, Alfred Marshall, Frank Knight (Bouldingās teacher), and Ronald Coase. We seek to demonstrate Penroseās connection to this āinvisible collegeā, particularly to Knight, and its influence on her investigation of the growth of the firm. Given mainstream economistsā pursuit of rigor at the expense of practical relevance and their continuing inattention to Coaseās work, we suggest Penroseās work on the growth of the firm can be understood as part of a broader tradition represented by this āinvisible collegeā, lending to useful new insights for business strategy and business ethics scholarship
Edith T. Penrose: Economist of "The Ordinary Business of Life"
When Edith T. Penrose became Fritz Machlupās student in the late-1940s, she found little in mainstream or Austrian economics to guide her as she began her explorations into the growth of the firm. While she acknowledged Kenneth Bouldingās influence on her work, we suspect she drew on a broader tradition that includes, among others, Alfred Marshall, Frank Knight (Bouldingās teacher), and Ronald Coase. We seek to demonstrate Penroseās connection to this āinvisible collegeā, particularly to Knight, and its influence on her investigation of the growth of the firm. Given mainstream economistsā pursuit of rigor at the expense of practical relevance and their continuing inattention to Coaseās work, we suggest Penroseās work on the growth of the firm can be understood as part of a broader tradition represented by this āinvisible collegeā, leading to useful new insights for business strategy and business ethics scholarship
Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas
Background: TGF-Ī² induces apoptosis in Burkitt's lymphoma cells.
Results: PUMA is a direct target gene of TGF-Ī² signaling and is required for rapid apoptosis.
Conclusion: TGF-Ī²-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas.
Significance: These studies link TGF-Ī² signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival
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 ālesbian gender,ā 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 Ī² Superfamily Type 1 Receptors.
The transforming growth factor Ī² (TGFĪ²) superfamily includes TGFĪ², 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 TGFĪ² 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 Ī² receptor 1 (TGFBR1) kinase inhibitors designed to target TGFĪ² 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 TGFĪ²-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 TGFĪ²-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 TGFĪ²- and BMP-regulated signaling pathways to disease states
Female sex but not oestrogen receptor expression predicts survival in advanced gastroesophageal adenocarcinomaāa post-hoc analysis of the go2 trial
Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) Ī± and Ī². In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52ā90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERĪ±, compared to 70.6% for ERĪ² expression. There was no survival impact according to ERĪ² expression level. Female sex and younger age were associated with lower ERĪ² expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age
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