The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to (...) UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

Ran is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras‐like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in both its (...) nuclear localization, and its lack of sites required for post‐translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions. (shrink)

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

In this essay, I claim that certain passages in Book IV of Benedict de Spinoza’s Ethics suggest a novel version of what is known as metaethical constructivism. The constructivist interpretation emerges in the course of attempting to resolve a tension between Spinoza’s apparent ethical egoism and some remarks he makes about the efficacy of collaborating with the right partners when attempting to promote our individual self-interest . Though Spinoza maintains that individuals necessarily aim to promote their self-interest, I argue that (...) Spinoza has an atypical conception of self that allows the interests of other people to be partially constitutive of one's own self-interest. In this way, Spinoza can account for the rationality of concern for the interests of others . This interpretation attributes to Spinoza a form of constructivism that differs in important ways from contemporary Humean and Kantian constructivisms and which can in principle be detached from Spinoza’s particular metaphysical commitments in order to yield a third general category of constructivist view . Though my treatment is necessarily brief, it is my hope that it can serve both to motivate a constructivist reading of Spinoza and, perhaps even more crucially, to suggest a Spinozistic variety of constructivism as a live theoretical option in metaethics. (shrink)

We suggest that in the particular context of medical education, ethics can be considered in a similar way to other kinds of knowledge that are categorised and shaped by academics in the context of wider society. Moreover, the study of medical ethics education is translational in a manner loosely analogous to the study of medical education as adjunct to translational medicine. Some have suggested there is merit in the idea that much as translational research attempts to connect the laboratory scientist's (...) work to its implications for patient care, translational ethics focuses on bringing ethics scholarship into the sphere of personal and public action. We distinguish the term ‘translational ethics’ (the study of ethics being translated between academy, classroom and clinic) from other prominent definitions in the bioethics literature. To do this, we build off a notion of knowledge translation that focuses on the nonlinear movement of information that comes to professionals through multiple competing sources. We suggest that this knowledge, and particularly knowledge about ethics, becomes embodied by the individual. It is through a reflective practice that internally embedded ethics knowledge might be modified, and this work might be best carried out with a moral community that maintains a sense of practical wisdom. Applying this translational approach to the study of medical ethics education can be both academically relevant and practically useful. This view of translation can help bridge the evident, multidirectional relationships between research, education and performance. It might also create further opportunities to develop medical ethics education theory. (shrink)

Hegemony is one of the most widely diffused concepts in the contemporary social sciences and humanities internationally, interpreted in a variety of ways in different disciplinary and national contexts. However, its contemporary relevance and conceptual coherence has recently been challenged by various theories of ‘posthegemony’. This article offers a critical assessment of this theoretical initiative. In the first part of the article, I distinguish between three main versions of posthegemony – temporal, foundational and expansive – characterized by different understandings of (...) the temporal and logical implications of hegemony. I then offer a critical assessment of the shared presuppositions of these theories, including their ‘pre-Gramscianism’, their indebtedness to Laclau and Mouffe’s formulation of hegemony, and their characterization of hegemony in terms compatible with modern theories of sovereignty. I conclude by arguing that the contradictions and oversights of the debate on posthegemony encourage us to undertake a reassessment of the real historical complexity of hegemonic politics and its different traditions of conceptualization. (shrink)

There are many things that could be wrong with foundationalism. For example, some have claimed that a so‐called basic belief cannot be both 1) a reason for non‐basic beliefs and 2) such that it cannot be provided with at least prima facie justification.1 If something is a reason, they say, then that something has to be a proposition (or sufficiently proposition‐like) and if it is a proposition (or sufficiently proposition‐like), then it is the kind of thing that requires a reason (...) in order to be even prima facie justified.2 Another reason that some give for rejecting normative foundationalism is that it leads directly to skepticism.3 There is no way, they claim, to move from so‐called basic propositions (typically given as first person introspective reports) to “external world” propositions by employing normatively acceptable principles of reasoning.4 Still others have thought that the invention of a nonrea‐soned reason was as ad hoc as the invention of an unmoved mover.5. (shrink)

Immanuel Kant spent many of his younger years working on what are generally considered his masterpieces: the three _Critiques_. But his work did not stop there: in later life he began to reconsider subjects such as anthropology, and topics including colonialism, race and peace. In _Late Kant_, Peter Fenves becomes one of the first to thoroughly explore Kant's later writings and give them the detailed scholarly attention they deserve. In his opening chapters, Fenves examines in detail the various essays (...) in which Kant invents, formulates and complicates the thesis of 'radical evil' - a thesis which serves as the point of departure for all his later writings. _Late Kant_ then turns towards the counter-thesis of 'radical mean-ness', which states that human beings exist on earth for the sake of another species or race of human beings. The consequences of this startling thesis are that human beings cannot claim possession of the earth, but must rather prepare the earth for its rightful owners. _Late Kant _is the first book to develop the 'geo-ethics' of Kant's thought, and the idea that human beings must be prepared to concede their space for another kind of human. It is essential reading for anyone interested in the later works of Immanuel Kant. (shrink)

Research on abusive supervision is imbalanced in two ways. First, with most research attention focused on the destructive consequences of abusive supervision, there has been relatively little work on subordinate-related predictors of perceptions of abusive supervision. Second, with most research on abusive supervision centered on its main effects and the moderating effects of supervisor-related factors, there is little understanding of how subordinate factors can moderate the main effects of perceptions of abusive supervision on workplace outcomes. The current study aims to (...) advance knowledge of the roles of subordinates in the formation of and reactions to perceptions of abusive supervision. Specifically, based on victim precipitation theory, the authors examined subordinates’ personality traits and self-reports of task performance as antecedents of perceptions of abusive supervision. The results show that subordinates high in neuroticism or low in conscientiousness had high levels of perceived abusive supervision partially through their self-reported deleterious job performance. In addition, the authors investigated the moderating effect of subordinates’ personality on the relationship between perceptions of abusive supervision and subordinates’ interpersonal deviance. Consistent with trait activation theory, subordinates low in both agreeableness and extraversion were more likely to engage in deviant behaviors in response to perceptions of abusive supervision than subordinates high in either or both agreeableness and extraversion. (shrink)

As the Pyrrhonians made clear, reasons that adequately justify beliefs can have only three possible structures: foundationalism, coherentism, and infinitism. Infinitism—the view that adequate reasons for our beliefs are infinite and non-repeating—has never been developed carefully, much less advocated. In this paper, I will argue that only infinitism can satisfy two intuitively plausible constraints on good reasoning: the avoidance of circular reasoning and the avoidance of arbitrariness. Further, I will argue that infinitism requires serious, but salutary, revisions in our evaluation (...) of the power of reasoning. Thus, reasoning can not provide a basis for assenting to a proposition—where to assent to a proposition, p, means to believe that we know that p. A non-dogmatic form of provisional justification will be sketched. Finally, the best objections to infinitism, including those posed by the Pyrrhonians, will be shown (at least provisionally!) to be inadequate. (shrink)

That there is a heritable or familial component of susceptibility to chronic non‐communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non‐genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non‐imprinted genes but (...) also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non‐genomic transgenerational inheritance of ‘lifestyle’ disease and propose that the ‘developmental origins of disease’ phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens. BioEssays 29: 145–154, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

There is a wealth of data on the perceptual and cognitive capacities of infants strongly supporting early nativistic influences on development. Without considering these initial determinants, constructivist models of development are at best incomplete.

Uses Buddhist philosophy to discuss diversity as a value, one that can contribute to equity in a globalizing world.

Public health is concerned with how to improve the population’s health. At times, though, actions to improve the community’s health may collide with individual civil rights. For example, a public health response to a bioterrorism attack, such as smallpox, may require relaxing an individual’s due process protections to prevent the smallpox from spreading. This tension lies at the heart of public health policy. It also must be considered in discussing the concept of human rights in health.Proponents of incorporating the concept (...) of human rights in health emphasize the importance of both individual rights and collective rights. They argue that observing human rights is not only consistent with broad public health goals, but necessary to their attainment. To many human rights advocates, the concept is not limited to protecting against governmental intrusion. Accordingly, they emphasize the government’s obligation to promote attainment of human rights by, for instance, providing adequate health care. (shrink)

Public health is concerned with how to improve the population’s health. At times, though, actions to improve the community’s health may collide with individual civil rights. For example, a public health response to a bioterrorism attack, such as smallpox, may require relaxing an individual’s due process protections to prevent the smallpox from spreading. This tension lies at the heart of public health policy. It also must be considered in discussing the concept of human rights in health.Proponents of incorporating the concept (...) of human rights in health emphasize the importance of both individual rights and collective rights. They argue that observing human rights is not only consistent with broad public health goals, but necessary to their attainment. To many human rights advocates, the concept is not limited to protecting against governmental intrusion. Accordingly, they emphasize the government’s obligation to promote attainment of human rights by, for instance, providing adequate health care. (shrink)

“Real knowledge,” as I use the term, is the most highly prized form of true belief sought by an epistemic agent. This paper argues that defeasible infinitism provides a good way to characterize real knowledge and it shows how real knowledge can arise from fallible justification. Then, I argue that there are two ways of interpreting Ernest Sosa's account of real knowledge as belief that is aptly formed and capable of being fully defended. On the one hand, if beliefs are (...) aptly formed only if they have a specific causal etiology, namely that they are efficiently caused fully or partially by virtuous characteristics of the epistemic agent, then Sosa's account falls prey to what I call the problem of the Hazard of Empirical Disconfirmation. The HED problem applies to all forms of causal accounts of real knowledge and is simply that as we gain more empirical knowledge about the causal origins of our true beliefs that are the most highly prized we will discover that they do not always satisfy the required efficient causal constraints. Bluntly put, having sufficiently good reasons for our beliefs might not require that the beliefs have the requisite efficient causal etiology. On the other hand, there is a way of interpreting Sosa's views that does not include an efficient causal prerequisite. That interpretation makes Sosa's account of real knowledge almost identical to defeasible infinitism but expressed in an alternate vocabulary. Such a view is not subject to the HED problem and it can solve the deep problem in epistemology, namely how to get epistemically certain knowledge from fallible justification. (shrink)

O propósito deste artigo é mostrar como podem ser desenvolvidas explicações robustas de justificação e de certeza no interior do infinitismo. Primeiro, eu explico como a concepção infinitista de justificação epistêmica difere das concepções fundacionista e coerentista. Em segundo lugar, explico como o infinitista pode oferecer uma solução ao problema do regresso epistêmico. Em terceiro lugar, explico como o infinitismo, per se, é compatível com as teorias daqueles que sustentam 1) que o conhecimento requer certeza e que uma tal forma (...) superior de conhecimento é possível, bem como com as daqueles que rejeitam algum ou ambos os conjuntos em 1). Em outras palavras, o infinitismo nem endossa, nem rejeita o ceticismo, tomando-se essa tese como sendo aquela segundo a qual nós não possuímos conhecimento naquelas situações que nos parecem cognoscíveis. PALAVRAS-CHAVE – Certeza. Coerentismo. Fundacionismo. Infinitismo. Pirronismo. Regresso epistêmico. ABSTRACT The purpose of the paper is to show how robust accounts of justification and certainty can be developed within infinitism. First, I explain how the infinitist conception of epistemic justification differs from both the foundationalist and coherentist conceptions. Second, I explain how the infinitist can provide a solution to the epistemic regress problem. Third, I explain how infinitism, per se, is compatible with both the views of those who hold 1) that knowledge requires certainty and that such high-grade knowledge is possible as well as those who deny either or both conjuncts in 1). In other words, infinitism neither endorses nor rejects skepticism, taking that view to mean that we do not have knowledge in those areas commonly thought to be within our ken. KEY WORDS – Certainty. Coherentism. Foundationalism. Infinitism. Pyrrhonism. Epistemic regress. (shrink)

An ongoing debate among legal scholars and public health advocates is the role of litigation in shaping public policy. For the most part, the debate has been waged at a conceptual level, with opponents and proponents arguing within fairly well-defined boundaries. The debate has been based either on speculation of what litigation could achieve or on ideological grounds as to why litigation should or should not be used this way. With the exception of Rosenberg's study of how litigation shaped policy (...) in civil rights, abortion, and environmental matters, there is almost no empirical support for either position.In recent years, the most ardent proponents of litigation as public policy have been public health advocates. Perhaps out of frustration with the inability to achieve desired public health goals through the legislative branch of government, public health advocates have pursued litigation as an alternative strategy. Beginning with tobacco class action litigation in the early 1990s and continuing with litigation against gun manufacturers at the end of that decade, public health advocates have waged a veritable litigation assault aimed at changing how public health policy is formed. (shrink)

An ongoing debate among legal scholars and public health advocates is the role of litigation in shaping public policy. For the most part, the debate has been waged at a conceptual level, with opponents and proponents arguing within fairly well-defined boundaries. The debate has been based either on speculation of what litigation could achieve or on ideological grounds as to why litigation should or should not be used this way. With the exception of Rosenberg's study of how litigation shaped policy (...) in civil rights, abortion, and environmental matters, there is almost no empirical support for either position.In recent years, the most ardent proponents of litigation as public policy have been public health advocates. Perhaps out of frustration with the inability to achieve desired public health goals through the legislative branch of government, public health advocates have pursued litigation as an alternative strategy. Beginning with tobacco class action litigation in the early 1990s and continuing with litigation against gun manufacturers at the end of that decade, public health advocates have waged a veritable litigation assault aimed at changing how public health policy is formed. (shrink)