Reason, Morality, and Skill

Some economists argue that modern industrial societies must respond to ecological challenges by learning to live with diminishing economic growth. Yet it also seems that low growth societies are doomed to struggle with problems of social instability caused by economic recession, unemployment and a decline in social entitlements. In “Reason, Morality and Skill” John Stopford draws on Ancient Greek economic thought, including Aristotle’s views on the natural limitation of wealth, to discuss the problem of human flourishing in ecologically challenged societies. Economic capability theorists, influenced by the work of Sen and Nussbaum, have recently argued that the transition from a growth driven economy focused on consumption to a stable low growth economy requires us to redefine prosperity as capability development “within limits”. Stopford argues that to understand prosperity in this way we need to reexamine the role of skill in the development of capabilities. The marginalization of skill has become a systematic feature of modern industrial and consumer societies. Yet certain kinds of skill, exemplified in the work of the autonomously productive craftsman, are necessary to the development of the bounded capabilities that low growth societies need to foster

Adorno's Critique of Judgement: the recovery of negativity from the philosophies of Kant and Hegel

This thesis has four primary aims. Firstly, I develop an account of Adorno’s critique of Kant and Hegel’s philosophy. I argue that the role and structure of judgement is key to his critical analysis. Adorno's discussion of their metaphysics, epistemology revolves around an immanent critique of judgement. This critique reveals, in the dialectical sense, the irreducibility of the 'negative moment' within judgement. This critical exposition grounds the second aim of the thesis. Analysis of Kant and Hegel's philosophies enables us to discern a number of key concepts in Adorno's own thought, concepts which will help us to understand his notion of negativity. In particular, his dialectical critique produces a constellation of critical - or negative - dialectical concepts: conceptless [begriffslose], non-identity [Nichtidentität], mediation [Vermittlung]. The generation of these concepts and their elucidation provides the basis for the third aim: to give a textually viable and philosophically fruitful explanation of key commitments in Adorno’s negative dialectics. I argue that negative dialectics does not amount to a system, a standpoint, or even a set of principles. Rather, it is a critical activity. The commitments, which revolve around the constellation of concepts outlined above, indicate a critical sensitivity to the limits of epistemology and metaphysics and the problem that these limits pose for judgement. Finally, I develop the resources to answer Michael Rosen’s claim that Adorno’s rejection of Hegelian determinate negation leaves his dialectics without any dynamic force. Drawing upon aesthetics, we can better understand the dynamics of negative dialectics. Aesthetic engagement with artworks not only demonstrates an appropriate orientation of philosophy to material, it is also an appropriate medium through which we can gain a clearer understanding of the philosophical commitments elucidated above

Discrete mode laser diodes with ultra narrow linewidth emission <3kHz

Ex-facet, free-running ultra-low linewidth (<3 kHz), single mode laser emission is demonstrated using low cost, regrowth-free ridge waveguide discrete mode Fabry-Perot laser diode chips

Kaposi’s Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory Cytokine Expression in Human Monocytes

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with the human malignancy Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes lytic infection of monocytes in vivo , which may represent an important cellular reservoir during KS disease progression. KS tumors consist of latently infected endothelial cells; however, lytic phase gene products are important for KS onset. Early KS lesion progression is driven by proinflammatory cytokines supplied by immune cell infiltrates including T cells and monocytes. KSHV-infected monocytes may supply the lytic viral products and the inflammatory milieu conducive to KS tumor progression. To establish successful infection, KSHV extensively modulates the host immune system. KSHV antigens activate both innate and adaptive immune responses including KSHV-specific T cells, but lifelong infection is still established. Programmed death ligand 1 (PD-L1) is a prosurvival cell surface protein that suppresses T-cell-mediated killing. PD-L1 is variably present on various tumor cells and is a targetable marker for cancer treatment. We show that KSHV infection of human monocytes increases PD-L1 expression and transcription in a dose-dependent manner. We also saw evidence of lytic gene expression in the KSHV-infected monocytes. Intact KSHV is needed for full PD-L1 response in human monocytes. KSHV induces a general proinflammatory cytokine milieu including interleukins 1α, 1β, and 6, which have been implicated in early KS lesion progression. KSHV-mediated PD-L1 increase may represent a novel mechanism of KSHV-mediated immune modulation to allow for virus survival and eventually malignant progression. IMPORTANCE KSHV is the etiologic agent of Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. Programmed death ligand 1 (PD-L1) is an immunosuppressive cell surface marker that inhibits T cell activation. We report that KSHV infection of primary human monocytes upregulates PD-L1 transcription and protein expression. Analysis of the cytokine and chemokine milieu following KSHV infection of monocytes revealed that KSHV induces interleukins 1α, 1β, and 6, all of which have been implicated in KS development. Our work has identified another potential immune evasion strategy for KSHV and a potential target for immunotherapy of KSHV-derived disease

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 1 Interacts with a Member of the Interferon-Stimulated Gene 15 Pathway

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus known to establish lifelong latency in the human host. We and others have previously shown that three KSHV homologs of cellular interferon regulatory factors (IRFs), known as viral IRFs (vIRFs), participate in evasion of the host interferon (IFN) response. We report that vIRF1 interacts with the cellular interferon-stimulated gene 15 (ISG15) E3 ligase, HERC5, in the context of Toll-like receptor 3 (TLR3) activation and IFN induction. The ISG15 protein is covalently conjugated to target proteins upon activation of the interferon response. Interaction between vIRF1 and HERC5 was confirmed by immunoprecipitation, and the region between amino acids 224 and 349 of vIRF1 was required for interaction with HERC5. We further report that expression of vIRF1 in the context of TLR3 activation results in decreased ISG15 conjugation of proteins. Specifically, TLR3-induced ISG15 conjugation and protein levels of cellular IRF3, a known ISG15 target, were decreased in the presence of vIRF1 compared to the control. vIRF1 itself was also identified as a target of ISG15 conjugation. KSHV-infected cells exhibited increased ISG15 conjugation upon reactivation from latency in coordination with increased IFN. Furthermore, knockdown of ISG15 in latently infected cells resulted in a higher level of KSHV reactivation and an increase in infectious virus. These data suggest that the KSHV vIRF1 protein affects ISG15 conjugation and interferon responses and may contribute to effective KSHV replication. IMPORTANCE The KSHV vIRF1 protein can inhibit interferon activation in response to viral infection. We identified a cellular protein named HERC5, which is the major ligase for ISG15, as a vIRF1 binding partner. vIRF1 association with HERC5 altered ISG15 modification of cellular proteins, and knockdown of ISG15 augmented reactivation of KSHV from latency

Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a DNA virus that is linked to several human malignancies. The cGMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is able to detect KSHV during primary infection and regulates the reactivation of KSHV from latency. We screened KSHV proteins for their ability to inhibit this pathway and block IFN-β activation. One KSHV protein, vIRF1, inhibited this pathway by preventing STING from interacting with TBK1 and inhibiting STING’s phosphorylation and concomitant activation. Moreover, depletion of vIRF1 in the context of KSHV infection prevented efficient viral reactivation and replication, and increased the host IFN response to KSHV. Collectively, our results demonstrate that the modulation of this pathway is important for viral transmission and the lifelong persistence of gammaherpesviruses in the human population

Are Foreign Firms Privileged By Their Host Governments? Evidence From The 2000 World Business Environment Survey

Using the data from World Business Environment Survey (WBES) on over 10,000 firms across eighty one countries, this paper finds preliminary evidence that foreign firms enjoy significant regulatory advantages - as perceived by the firms themselves - over domestic firms. The findings on regulatory advantages of foreign firms hold with a variety of alternative measures of regulations and with or without firm- and country-level attributes and industry and country controls. There is also evidence that foreign firms' regulatory advantages are especially substantial vis-a-vis the politically weak domestic firms. Furthermore, the regulatory advantages of foreign firms appear stronger in corrupt countries than in non-corrupt countries

Moral Realism and Political Decisions. Practical Rationality in Contemporary Public Contexts

The challenge of realism is one of the common features of current philosophical debates, across different cultural traditions, and in many areas of investigation (epistemology, metaphysics, ethics, aesthetics, theory of action, etc.). The implications of realism for political philosophy and political practice, though, are just starting to become an object of systematic discussions. Such implications, however, are significant, since the area of politics is contiguous with that of ethics and action, for example. This volume intends to contribute to debates on the relevance of realism – especially moral realism – for politics. The essays included in the collection address a number of related issues, ranging from foundational problems of realism in ethics, action theory and politics, to questions about pragmatics, to difficulties in political theory, and to political hindrances related to economics and legal theory. The common focus of all essays is the relevance of realism for a conception of practical rationality in political contexts.Die Herausforderungen, vor die uns der Realismus stellt, sind in aktuellen philosophischen Debatten gegenwärtig und sie machen sich durch unterschiedliche kulturelle Traditionen und viele Untersuchungsbereiche (Erkenntnistheorie, Metaphysik, Ethik, Ästhetik, Handlungstheorie, etc.) hindurch bemerkbar. Die Auswirkungen des Realismus auf die Politische Philosophie und die politische Praxis sind jedoch erst seit kurzem Gegenstand systematischer Diskussionen, obwohl sie von Bedeutung sind, denn letztlich steht der Bereich der Politik immer in einem Zusammenhang mit Fragen der Ethik und der Handlung. Dieser Band möchte einen Beitrag zu den Debatten über die Relevanz des Realismus für die Politik leisten und hat dabei insbesondere den moralischen Realismus im Blick. Die hier versammelten Aufsätze enthalten eine Reihe von Auseinandersetzungen mit damit zusammenhängenden Problemstellungen, die von grundlegenden Problemen des Realismus in der Ethik, Handlungstheorie und Politik, Fragen zur Pragmatik, über die Schwierigkeiten der Politischen Theorie, bis hin zu politischen Hindernissen für Wirtschaft und Recht reichen. Der gemeinsame Fokus aller Aufsätze liegt dabei in der Betrachtung der Relevanz eines Realismus‘ für eine Konzeption einer praktischen Vernunft im politischen Kontext