Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

First published in 2000. Routledge is an imprint of Taylor & Francis, an informa company.

ABSTRACTThe political is changing its shape. Ideologies are no longer stable, but instead build hybrid combinations. Populism is getting popular. In addition, there are new forms of political exper...

This study examines how institutional logics interplay in a cross-sector social partnership that manages refugee integration in a rural district in Germany. In an inductive 15-month case study that drew on interviews and observations, we observe the dynamic materialization of institutional logics in day-to-day practices and an increasing contradiction and even rivalry between community- and market-based institutional logics over time. As a result, we delineate a model explaining the interplay of institutional logics along two dimensions: the dominance of one salient (...) logic and whether conflicts arise among logics. Our analysis also addresses the unifying properties of community as an institutional logic, especially in the context of urgency conditions. In addition, we show the influence of exogenous events and their media coverage on the interplay and conflicts of institutional logics. By unfolding the complexity of refugee integration—one of the global grand challenges of the present—we deepen the current understanding of the specific challenges addressed by cross-sector social partnerships. (shrink)

Frank Ramsey was the greatest of the remarkable generation of Cambridge philosophers and logicians which included G. E. Moore, Bertrand Russell, Ludwig Wittgenstein and Maynard Keynes. Before his tragically early death in 1930 at the age of twenty-six, he had done seminal work in mathematics and economics as well as in logic and philosophy. This volume, with a new and extensive introduction by D. H. Mellor, contains all Ramsey's previously published writings on philosophy and the foundations of mathematics. The (...) latter gives the definitive form and defence of the reduction of mathematics to logic undertaken in Russell and Whitehead's Principia Mathematica; the former includes the most profound and original studies of universals, truth, meaning, probability, knowledge, law and causation, all of which are still constantly referred to, and still essential reading for all serious students of these subjects. (shrink)

This article rebuts Ramsey's earlier theory, in 'Universals of Law and of Fact', of how laws of nature differ from other true generalisations. It argues that our laws are rules we use in judging 'if I meet an F I shall regard it as a G'. This temporal asymmetry is derived from that of cause and effect and used to distinguish what's past as what we can know about without knowing our present intentions.

Managers tasked with organizational change often face irreconcilable demands on how to enact justice—situations we call _justice conundrums_. Drawing on interviews held with managers before and after a planned large-scale change, we identify specific conundrums and illustrate how managers grapple with these through three prototypical paths. Among our participants, the paths increasingly diverged over time, culminating in distinct career decisions. Based on our findings, we develop an integrative process model that illustrates how managers grapple with justice conundrums. Our contributions are (...) threefold. First, we elucidate three types of justice conundrums that managers may encounter when enacting justice in the context of planned organizational change (the justice intention-action gap, competing justice expectations, and the justice of care vs. managerial-strategic justice) and show how managers handle them differently. Second, drawing on the motivated cognition and moral disengagement literature, we illustrate how cognitive mechanisms coalesce to allow managers to soothe their moral (self-) concerns when grappling with these conundrums. Third, we show how motivated justice intentions ensuing from specific justice motives, moral emotions, and circles of moral regard predict the types of justice conundrums managers face and the paths they take to grapple with them. (shrink)

Although we can observe noticeable progress in gender diversity on corporate boards, these boards remain far from gender balanced. Our paper builds on social identity theory to examine the impact of corporate elites—men and women who sit on multiple corporate boards—on board diversity. We extend the main argument of social identity theory concerning favouritism based on homophily by suggesting that boards with men with multiple appointments are unwilling to include female board members to protect the monopoly value generated by their (...) elite status. The empirical analysis, based on DAX 30 firms in the period of 2010–2015, shows that the presence of multi-board men is negatively associated with women’s participation, while the presence of multi-board women and other women on management boards is positively related to gender diversity on boards. Furthermore, robustness tests support and confirm our conclusion that multi-board men have a significant association with board diversity, even with small size. Additionally, we find a significant effect arising from pressure related to the introduction of gender quotas in Germany, effective in 2016, indicating the effectiveness of gender quota policies for board gender diversity. (shrink)

In recent years, millions of citizens all over the world have used digital dating services. It remains unknown to what extent human sexuality will be changed by this. Based on an evolutionary psychological perspective, we assume that sexual selection shaped behavioural tendencies in men and women that are designed to increase the reproductive fitness. These tendencies are referred to as sexual strategies. Males and females sexual strategies differ according to sex-dimorphic reproductive investments. We assume that this inheritance will affect human (...) sexuality also in a digital future. To evaluate this assumption, we conducted a selective review of studies on digital dating services. Based on sexual selection theory, we derived a number of hypotheses regarding how men and women will use digital dating services typically and how the use of digital dating services might affect sexual wellbeing. Out of an initial data set of 2,568 records, we finally reviewed a set of 13 studies. These studies provided support for the notion that men and women act in the digital dating area according to sex-typical strategies. However, sometimes the circumstances of digital dating affect communication flow, e.g., in that men are even more active in establishing contacts than they are in real world conditions. Overall, women appear to accomplish their sexual goals in digital dating arenas more than men do given a surplus of male demand. Our results suggest that future human sexuality will be impacted by an interaction of both: sex-dimorphic ancient sexual strategies and new technologies. (shrink)

We attempt to extend the nominalistic project initiated in Hartry Field's Science Without Numbers to modern physical theories based in differential geometry.

Space, Time, and Stuff is an attempt to show that physics is geometry: that the fundamental structure of the physical world is purely geometrical structure. Along the way, he examines some non-standard views about the structure of spacetime and its inhabitants, including the idea that space and time are pointless, the idea that quantum mechanics is a completely local theory, the idea that antiparticles are just particles travelling back in time, and the idea that time has no structure whatsoever. The (...) main thrust of the book, however, is that there are good reasons to believe that spaces other than spacetime exist, and that it is the existence of these additional spaces that allows one to reduce all of physics to geometry. Philosophy, and metaphysics in particular, plays an important role here: the assumption that the fundamental laws of physics are simple in terms of the fundamental physical properties and relations is pivotal."--P. [4] of cover. (shrink)

The Metaphysical Club, a gathering of intellectuals in the 1870s associated with Harvard, is widely recognized as the crucible where pragmatism, America's distinctively original philosophy, was refined and proclaimed. Louis Menand's bestseller about the group was a dramatic publishing success. However, only three actual members - Oliver Wendell Holmes Jr., Charles S. Peirce, and William James - appear in this book, alongside other thinkers such as John Dewey who were never in the Club. The Real Metaphysical Club tells the full (...) story of how this influential group shifted the course of philosophy in America. In addition to pioneering pragmatism, the group explored radical empiricism and idealism, and formulated personalism and process philosophy, equally important developments. This volume contains thirty-seven important writings dating from 1870 to 1885 by the real members of the Metaphysical Club. The first section centers on pragmatism and science; the second part collects writings of the lawyers; and the third part covers idealist and personalist philosophers. Many of these writings have never been reprinted before, and nothing like this impressive collection has ever been attempted. A general introduction provides a narrative history, and the editors' three introductions to the volume's sections vividly bring to life the intense meetings, sustained debates, and pioneering thought from the Metaphysical Club. (shrink)

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine (...) data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented. (shrink)

I argue that it may well be the case that space and time do not consist of points, indeed that they have no smallest parts. I examine two different approaches to such pointless spaces : a topological approach and a measure theoretic approach. I argue in favor of the measure theoretic approach.

Suppose that two geysers, about one mile apart, erupt at irregular intervals, but usually erupt almost exactly at the same time. One would suspect that they come from a common source, or at least that there is a common cause of their eruptions. And this common cause surely acts before both eruptions take place. This idea, that simultaneous correlated events must have prior common causes, was first made precise by Hans Reichenbach (Reichenbach 1956). It can be used to infer the (...) existence of unobserved and unobservable events, and to infer causal relations from statistical relations. Unfortunately it does not appear to be universally valid, nor is there agreement as to the circumstances in which it is valid. (shrink)

This note is a postscript to Ramsey's 'Truth and Probability'. It replaces that article's psychological reading of subjective probability with a reading of it as a consistency condition on the theory that we act to maximise expected utility.

European Journal of Philosophy, Volume 30, Issue 2, Page 676-692, June 2022.

The common cause principle states that correlations have prior common causes which screen off those correlations. I argue that the common cause principle is false in many circumstances, some of which are very general. I then suggest that more restricted versions of the common cause principle might hold, and I prove such a restricted version.

Although the literature on organizational justice enactment is becoming richer, our understanding of the role of the deontic justice motive remains limited. In this article, we review and discuss theoretical approaches to and evidence of the deontic justice motive and deontic justice enactment. While the prevalent understanding of deontic justice enactment focuses on compliance, we argue that this conceptualization is insufficient to explain behaviors that go beyond the call of duty. We thus consider two further forms of deontic behavior: humanistic (...) and supererogatory behavior. Drawing on the concepts of situation strength and person strength, we further argue that the reduced variance in behavior across morally challenging situations makes deontic justice enactment visible. We thus observe deontic justice enactment when an actor’s deontic justice motive collides with strong situational cues or constraints that guide the actor to behave differently. We formulate propositions and develop a theoretical model that links the deontic justice motive to moral maturation and deontic justice enactment. (shrink)

According to ontological nihilism there are, fundamentally, no individuals. Both natural languages and standard predicate logic, however, appear to be committed to a picture of the world as containing individual objects. This leads to what I call the \emph{expressibility challenge} for ontological nihilism: what language can the ontological nihilist use to express her account of how matters fundamentally stand? One promising suggestion is for the nihilist to use a form of \emph{predicate functorese}, a language developed by Quine. This proposal faces (...) a difficult objection, according to which any theory in predicate functorese will be a notational variant of the corresponding theory stated in standard predicate logic. Jason Turner (2011) has provided the most detailed and convincing version of this objection. In the present paper, I argue that Turner's case for the notational variance thesis relies on a faulty metasemantic principle and, consequently, that an objection long thought devastating is in fact misguided. (shrink)