Normative Commitments in Metanormative Theory

First-order normative theories concerning what’s right and wrong, good and bad, etc. and metanormative theories concerning the nature of first-order normative thought and talk are widely regarded as independent theoretical enterprises. This paper argues that several debates in metanormative theory involve views that have first-order normative implications, even as the implications in question may not be immediately recognizable as normative. I first make my claim more precise by outlining a general recipe for generating this result. I then apply this recipe to three debates in metaethics: the modal status of basic normative principles, normative vagueness and indeterminacy, and the determination of reference for normative predicates. In each case I argue that certain views on each issue carry first-order normative commitments, in accordance with my recipe

Doubts about Moral Perception

This chapter defends doubts about the existence of genuine moral perception, understood as the claim that at least some moral properties figure in the contents of perceptual experience. The doubts are local: even if perceptual experiences generally can be cognitively penetrable and rich, standard examples of moral perception are better explained as habitual implicit inferences or transitions in thought. The chapter sketches a model on which the relevant transitions in thought can be psychologically immediate depending on how readily and reliably non-evaluative perceptual inputs, jointly with the subject’s background moral beliefs, training, and habituation, trigger the kinds of phenomenological responses that moral agents are disposed to have when they represent things as being morally a certain way. It is then argued that this rival account of moral experience explains at least as much as the moral perception hypothesis but is simpler and (at least by one relevant measure) more unified

The Supervenience Challenge to Non-Naturalism

It is impossible that one action is morally impermissible and another permissible unless they dier also in some other respect; perhaps one involves stealing but the other doesn’t. One person cannot be morally better or more virtuous than another without there being some other dierence between them, such as that one is more reliably disposed to help others or to keep her promises. It cannot be that you have a reason to run for the bus on one occasion but no reason to do so on another if the situations dier in no other qualitative respect, such as how ecient each action will be for achieving your aims or for doing something good. If two persons are qualitatively exactly alike (or “indiscernible”) in all other ways, they cannot but be morally alike as well

Significant Role of Collagen XVII And Integrin beta 4 in Migration and Invasion of The Less Aggressive Squamous Cell Carcinoma Cells

Collagen XVII and integrin alpha 6 beta 4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin alpha 6 beta 4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin.2, collagen XVII and integrin beta 4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen's disease. The expression of laminin.2 was highest in SCC samples, whereas the expression of collagen XVII and integrin beta 4 varied greatly in SCC and its precursors. Collagen XVII and integrin beta 4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin beta 4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin beta 4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin beta 4 contribute to SCC tumorigenesis.Peer reviewe

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Significant Role of Collagen XVII And Integrin β4 in Migration and Invasion of The Less Aggressive Squamous Cell Carcinoma Cells

Collagen XVII and integrin alpha 6 beta 4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin alpha 6 beta 4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin.2, collagen XVII and integrin beta 4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen's disease. The expression of laminin.2 was highest in SCC samples, whereas the expression of collagen XVII and integrin beta 4 varied greatly in SCC and its precursors. Collagen XVII and integrin beta 4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin beta 4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin beta 4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin beta 4 contribute to SCC tumorigenesis

What does regional studies study? From subnational to supra-national regional spaces or Grossraum of sovereign governance

This article makes a case for expanding the scope of current versions of “regional studies” to include greater emphasis upon transnational regions as of equal if not greater importance compared with an exclusive focus upon sub-national regions. The latter more restrictive approach is typically predicated on the continued centrality of state borders against which the dominant notion of regions as subnational entities is constituted and reiterated. Drawing upon a case study of the African Union our study provides a framework, a critically revised Grossraum theory, for addressing the emergence of a new pluralistic and multipolar world order characterised by supra-national regions and regional organizations. Traditional Schmittian notions of Grossraum are shown to be in need of substantial revision before they are able to adequately accommodate and explain the empirical details of our case study

The type-B moral error theory

I introduce a new version of Moral Error Theory, which I call Type-B Moral Error Theory. According to a Type-B theorist there are no facts of the kind required for there to be morality in stricto sensu, but there can be irreducible ‘normative’ properties which she deems, strictly speaking, to be morally irrelevant. She accepts that there are instrumental all things considered oughts, and categorical pro tanto oughts (both of which she deems morally irrelevant), but denies that there are categorical all things considered oughts on pain of requiring ‘queer’ facts to obtain. I detail the most central motivation of this version of the theory against its more traditional rival, according to which there are no irreducible normative properties at all. The motivation is that it, unlike its rival, can successfully be defended against the notorious charge of self-defeat

IL-17/Th17 Pathway Is Activated in Acne Lesions

Peer reviewe