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.

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 (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; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes. PRO thus serves as a tool for referencing protein entities at any level of specificity. To enhance this ability, and to facilitate the comparison of such entities described in different resources, we developed a standardized representation of proteoforms using UniProtKB as a sequence reference and PSI-MOD as a post-translational modification (...) reference. We illustrate its use in facilitating an alignment between PRO and Reactome protein entities. We also address issues of scalability, describing our first steps into the use of text mining to identify protein-related entities, the large-scale import of proteoform information from expert curated resources, and our ability to dynamically generate PRO terms. Web views for individual terms are now more informative about closely-related terms, including for example an interactive multiple sequence alignment. Finally, we describe recent improvement in semantic utility, with PRO now represented in OWL and as a SPARQL endpoint. These developments will further support the anticipated growth of PRO and facilitate discoverability of and allow aggregation of data relating to protein entities. (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)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a framework (...) for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Résumé Si l’absence de moralité des psychopathes a été largement étudiée, il existe peu de recherches sur leurs capacités esthétiques. Pourtant, beaucoup d’études cliniques de cas montrent qu’ils présentent un grave déficit dans ce domaine. Cet article se propose d’en chercher les causes. Il analyse les forces et les limites de l’hypothèse d’un manque d’empathie pour expliquer ces carences esthétiques, et montre pourquoi l’hypothèse d’un manque de distance psychique se révèle plus féconde. Celle-ci permet en outre de comprendre le lien (...) de l’esthétique et de l’éthique par leur filiation commune : elles ont pour socle commun la capacité à prendre de la distance par rapport à des intérêts étroitement égoïstes. (shrink)

Discerning the decisionmaking of Kim Jong-Un and the North Korean regime on issues of peaceful engagement and warlike actions endures as a mighty challenge for U.S. intelligence analysts and policymakers. In this report, we seek to inform analysis of Democratic People’s Republic of Korea (DPRK) leadership decisionmaking. To do so, we use three discussion papers that were written to facilitate discussion of an interagency working group. The three papers are assembled here in a single report. The first discussion paper describes (...) decisionmaking among different authoritarian regimes, including North Korea, and the opening up of those economies to outside engagement. The second paper outlines two different scenarios that might occur when conventional deterrence on the Korean Peninsula breaks down and the resulting decisions that North Korea’s leadership could face. The third paper assesses DPRK decisionmaking about nuclear weapon use. The report concludes with some observations, drawn from the issues covered in these three discussion papers, about DPRK decisionmaking and stability on the Korean Peninsula. (shrink)

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create (...) new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. (shrink)

What happens when someone acts? A familiar answer goes like this. There is something that the agent wants, and there is an action that he believes conducive to its attainment. His desire for the end, and his belief in the action as a means, justify taking the action, and they jointly cause an intention to take it, which in turn causes the corresponding movements of the agent's body. I think that the standard story is flawed in several respects. The flaw (...) that will concern me in this paper is that the story fails to include an agent-or, more precisely, fails to cast the agent in his proper role. (shrink)

Supervaluationism is often described as the most popular semantic treatment of indeterminacy. There’s little consensus, however, about how to fill out the bare-bones idea to include a characterization of logical consequence. The paper explores one methodology for choosing between the logics: pick a logic thatnorms beliefas classical consequence is standardly thought to do. The main focus of the paper considers a variant of standard supervaluational, on which we can characterizedegrees of determinacy. It applies the methodology above to focus ondegree logic. (...) This is developed first in a basic, single-premise case; and then extended to the multipremise case, and to allowdegreesof consequence. The metatheoretic properties of degree logic are set out. On the positive side, the logic is supraclassical—all classical valid sequents are degree logic valid. Strikingly, metarules such as cut and conjunction introduction fail. (shrink)

In this volume, leading philosophers of psychiatry examine psychiatric classification systems, including the Diagnostic and Statistical Manual of Mental Disorders, asking whether current systems are sufficient for effective diagnosis, treatment, and research. Doing so, they take up the question of whether mental disorders are natural kinds, grounded in something in the outside world. Psychiatric categories based on natural kinds should group phenomena in such a way that they are subject to the same type of causal explanations and respond similarly to (...) the same type of causal interventions. When these categories do not evince such groupings, there is reason to revise existing classifications. The contributors all question current psychiatric classifications systems and the assumptions on which they are based. They differ, however, as to why and to what extent the categories are inadequate and how to address the problem. Topics discussed include taxometric methods for identifying natural kinds, the error and bias inherent in DSM categories, and the complexities involved in classifying such specific mental disorders as "oppositional defiance disorder" and pathological gambling. -/- Contributors George Graham, Nick Haslam, Allan Horwitz, Harold Kincaid, Dominic Murphy, Jeffrey Poland, Nancy Nyquist Potter, Don Ross, Dan Stein, Jacqueline Sullivan, Serife Tekin, Peter Zachar. (shrink)

This paper considers two reasons that might support Russell’s choice of a ramified-type theory over a simple-type theory. The first reason is the existence of purported paradoxes that can be formulated in any simple-type language, including an argument that Russell considered in 1903. These arguments depend on certain converse-compositional principles. When we take account of Russell’s doctrine that a propositional function is not a constituent of its values, these principles turn out to be too implausible to make these arguments troubling. (...) The second reason is conditional on a substitutional interpretation of quantification over types other than that of individuals. This reason stands up to investigation: a simple-type language will not sustain such an interpretation, but a ramified-type language will. And there is evidence that Russell was tacitly inclined towards such an interpretation. A strong construal of that interpretation opens a way to make sense of Russell’s simultaneous repudiation of propositions and his willingness to quantify over them. But that way runs into trouble with Russell’s commitment to the finitude of human understanding. (shrink)

Many believe that objective morality requires a theistic foundation. I maintain that there are sui generis objective ethical facts that do not reduce to natural or supernatural facts. On my view, objective morality does not require an external foundation of any kind. After explaining my view, I defend it against a variety of objections posed by William Wainwright, William Lane Craig, and J. P. Moreland.

Logicism is, roughly speaking, the doctrine that mathematics is fancy logic. So getting clear about the nature of logic is a necessary step in an assessment of logicism. Logic is the study of logical concepts, how they are expressed in languages, their semantic values, and the relationships between these things and the rest of our concepts, linguistic expressions, and their semantic values. A logical concept is what can be expressed by a logical constant in a language. So the question “What (...) is logic?” drives us to the question “What is a logical constant?” Though what follows contains some argument, limitations of space constrain me in large part to express my Credo on this topic with the broad brush of bold assertion and some promissory gestures. (shrink)

Contrary to economics or history, for example, there does not exist an organized field dedicated to the philosophy of political science. Given that the philosophical issues raised by political science research are just as pressing and vibrant as those raised in these more organized fields, fostering a field that labels itself Philosophy of Political Science (PoPS) is important. PoPS is advanced here as a fruitful meeting place where both philosophers and practicing political scientists contribute and discuss—with philosophical discussions that are (...) close to and informed by actual developments in political science, making philosophy of science continuous with the sciences in line with contemporary naturalist philosophy of science. The topics scrutinized in the different chapters of the Handbook will figure prominently in PoPS, as we lay out in this chapter. (shrink)

This paper has three aims: to define autonomism clearly and charitably, to offer a positive argument in its favour, and to defend a larger view about what is at stake in the debate between autonomism and its critics. Autonomism is here understood as the claim that a valuer does not make an error in failing to bring her moral and aesthetic judgements together, unless she herself values doing so. The paper goes on to argue that reason does not require the (...) valuer to make coherent her aesthetic and moral evaluations. Finally, the paper shows that the denial of autonomism has realist commitments that autonomism does not have, and concludes that issues of value realism and irrealism are relevant to the debates about autonomism in ways that have not hitherto been recognized. (shrink)

Discourse carries thin commitment to objects of a certain sort iff it says or implies that there are such objects. It carries a thick commitment to such objects iff an account of what determines truth-values for its sentences say or implies that there are such objects. This paper presents two model-theoretic semantics for mathematical discourse, one reflecting thick commitment to mathematical objects, the other reflecting only a thin commitment to them. According to the latter view, for example, the semantic role (...) of number-words is not designation but rather the encoding of cardinality-quantifiers. I also present some reasons for preferring this view. (shrink)

Immoralists hold that in at least some cases, moral fl aws in artworks can increase their aesthetic value. They deny what I call the valence constraint: the view that any effect that an artwork’s moral value has on its aesthetic merit must have the same valence. The immoralist offers three arguments against the valence constraint. In this paper I argue that these arguments fail, and that this failure reveals something deep and interesting about the relationship between cognitive and moral value. (...) In the fi nal section I offer a positive argument for the valence constraint. (shrink)

This paper and its sequel “look under the hood” of the usual sorts of proof-theoretic systems for certain well-known intuitionistic and classical propositional modal logics. Section 1 is preliminary. Of most importance: a marked formula will be the result of prefixing a formula in a propositional modal language with a step-marker, for this paper either 0 or 1. Think of 1 as indicating the taking of “one step away from 0.” Deductions will be constructed using marked formulas. Section 2 presents (...) the model-theoretic concepts, based on those in [7], that guide the rest of this paper. Section 3 presents Natural Deduction systems IK and CK, formalizations of intuitionistic and classical one-step versions of K. In these systems, occurrences of step-markers allow deductions to display deductive structure that is covered over in familiar “no step” proof-theoretic systems for such logics. Box and Diamond are governed by Introduction and Elimination rules; the familiar K rule and Necessitation are derived (i.e. admissible) rules. CK will be the result of adding the 0-version of the Rule of Excluded Middle to the rules which generate IK. Note: IK is the result of merely dropping that rule from those generating CK, without addition of further rules or axioms (as was needed in [7]). These proof-theoretic systems yield intuitionistic and classical consequence relations by the obvious definition. Section 4 provides some examples of what can be deduced in IK. Section 5 defines some proof-theoretic concepts that are used in Section 6 to prove the soundness of the consequence relation for IK (relative to the class of models defined in Section 2.) Section 7 proves its completeness (relative to that class). Section 8 extends these results to the consequence relation for CK. (Looking ahead: Part 2 will investigate one-step proof-theoretic systems formalizing intuitionistic and classical one-step versions of some familiar logics stronger than K.). (shrink)

Ancient Chinese and Greek thinkers alike were preoccupied with the moral value of music; they distinguished between good and bad music by looking at the music’s effect on moral character. The idea can be understood in terms of two closely related questions. Does music have the power to affect the ethical character of either listener or performer? If it does, is it better as music for doing so? I argue that an affirmative answers to both questions are more plausible than (...) it might seem at first. (shrink)

Biomedical science has been remarkably successful in explaining illness by categorizing diseases and then by identifying localizable lesions such as a virus and neoplasm in the body that cause those diseases. Not surprisingly, researchers have aspired to apply this powerful paradigm to addiction. So, for example, in a review of the neuroscience of addiction literature, Hyman and Malenka (2001, p. 695) acknowledge a general consensus among addiction researchers that “[a]ddiction can appropriately be considered as a chronic medical illness.” Like other (...) diseases, “Once addiction has taken hold, it tends to follow a chronic course.” (Koob and La Moal 2006, p. ?). Working from this perspective, much effort has gone into characterizing the symptomology of addiction and the brain changes that underlie them. Evidence for involvement of dopamine transmission changes in the ventral tegmental area (VTA) and nucleus accumbens (NAc) have received the greatest attention. Kauer and Malenka (2007, p. 844) put it well: “drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward processing”. Our goal in this chapter to provide an explicit description of the assumptions of medical models, the different forms they may take, and the challenges they face in providing explanations with solid evidence of addiction. <br>. (shrink)

A model-theoretic approach to the semantics of set-theoretic discourse.

According to a number of contemporary theorists, aesthetic reasons can invite or entice us but never compel us. In this paper, I develop a Kantian account of the normative force of aesthetic reasons. While Kant would likely agree that aesthetic reasons do not give rise to obligations, his account nevertheless gives us the resources for explaining how aesthetic reasons can still have more force than merely enticing reasons. This account appeals to the distinct normativity of aesthetic judgments on Kant's theory (...) and the way in which this kind of normativity structures aesthetic exchanges with other judging subjects. I argue that, in addition to the moral reasons we have for appreciating and preserving beauty, Kant’s account can accommodate distinctly aesthetic reasons for doing so that stem from our membership in aesthetic communities. (shrink)

El objetivo de este artículo es clarificar la noción de «vida auténtica» tal y como es descrita por Joan Roura-Parella en su última obra Tema y variaciones de la personalidad (1950). Por «vida auténtica» se entiende una vida autogobernada, que permite al individuo realizar su propia singularidad y, por tanto, preservar su autonomía y dignidad como persona. Una vida dominada por factores ajenos al propio individuo, sean cuales sean éstos, es una vida alienada, que no permite el desarrollo del individuo (...) en tanto la persona que es. Se señala la relevancia filosófica de la propuesta de Roura-Parella, que es la de ofrecer una justificación no-evidencial para una forma de vida cristiana, agapística. De acuerdo con Roura-Parella, una forma de vida basada en la entrega amorosa para con el prójimo está justificada en tanto que ésta es el resultado último de nuestra propia condición natural, constituyendo así un acto de afirmación personal y siendo, por tanto, condición necesaria para gozar de una vida auténtica — «la vida alcanza su hondo sentido al salirse de sí misma para darse a los demás» (Roura-Parella, Tema y variaciones de la personalidad, 1950, p. 229). Se señalan las diferencias y semejanzas de la propuesta de Roura-Parella con respecto a las de Miguel de Unamuno y Joaquim Xirau, autores que fueron cercanos a Roura-Parella y quienes, aunque partiendo de razonamientos distintos a los de Roura-Parella, también concibieron la entrega amorosa para con el prójimo como un acto de afirmación personal. (shrink)

Aesthetic internalism claims a link between judgement and motivation: aesthetic judgements bring with them motivations to act in characteristic ways. Critics object that there is a difference between merely liking something and judging it to be aesthetically good, and that it is our likings, not our aesthetic judgements, that motivate us. This paper develops a version of aesthetic internalism that can respond to this criticism. Wholehearted aesthetic judgements are characterized by stability, attention, and motivation. Making such judgements is an important (...) part of a good life, and so at least some aesthetic judgements are motivating. So we have reason to think that this version of aesthetic internalism is true. This paper defends wholehearted aesthetic internalism against objections, and assesses an argument from aesthetic internalism to aesthetic non-cognitivism. While wholehearted aesthetic internalism can only offer qualified support to non-cognitivism, it nonetheless offers a number of fruitful avenues for further work. (shrink)

Where $\underline{a}$ is a Turing degree and ξ is an ordinal $ , the result of performing ξ jumps on $\underline{a},\underline{a}^{(\xi)}$ , is defined set-theoretically, using Jensen's fine-structure results. This operation appears to be the natural extension through $(\aleph_1)^{L^\underline{a}}$ of the ordinary jump operations. We describe this operation in more degree-theoretic terms, examine how much of it could be defined in degree-theoretic terms and compare it to the single jump operation.

The topic of this essay is how non-realistic novels challenge our philosophical understanding of the moral significance of literature. I consider just one case: Joseph Heller’s Catch-22. I argue that standard philosophical views, based as they are on realistic models of literature, fail to capture the moral significance of this work. I show that Catch-22 succeeds morally because of the ways it resists using standard realistic techniques, and suggest that philosophical discussion of ethics and literature must be pluralistic if it (...) is to include all morally salient literature, and not just novels in the “Great Tradition” and their ilk. (shrink)

I prove that the Boolean Prime Ideal Theorem is equivalent, under some weak set-theoretic assumptions, to what I will call the Cut-for-Formulas to Cut-for-Sets Theorem: for a set F and a binary relation |- on Power(F), if |- is finitary, monotonic, and satisfies cut for formulas, then it also satisfies cut for sets. I deduce the CF/CS Theorem from the Ultrafilter Theorem twice; each proof uses a different order-theoretic variant of the Tukey- Teichmüller Lemma. I then discuss relationships between various (...) cut-conditions in the absence of finitariness or of monotonicity. (shrink)

Divers presents a set of de re modal truths which, he claims, are inconvenient for Lewisean modal realism. We argue that there is no inconvenience for Lewis.

I explore the claim that “fictive imagining” – imagining what it is like to be a character – can be morally dangerous. In particular, I consider the controversy over William Styron’s imagining the revolutionary protagonist in his Confessions of Nat Turner. I employ Ted Cohen’s model of fictive imagining to argue, following a generally Kantian line of thought, that fictive imagining can be dangerous if one has the wrong motives. After considering several possible motives, I argue that only internally directed (...) motives can satisfy the moral concern. Finally, I suggest that when one has the right motives, fictive imagining is morally praiseworthy since it improves one’s ability to imagine the lives of others. (shrink)

Part 1 [Hodes, 2021] “looked under the hood” of the familiar versions of the classical propositional modal logic K and its intuitionistic counterpart. This paper continues that project, addressing some familiar classical strengthenings of K and GL), and their intuitionistic counterparts. Section 9 associates two intuitionistic one-step proof-theoretic systems to each of the just mentioned intuitionistic logics, this by adding for each a new rule to those which generated IK in Part 1. For the systems associated with the intuitionistic counterparts (...) of D and T, these rules are “pure one-step”: their schematic formulations does not use □ or ♢. For the systems associated with the intuitionistic counterparts of K4, etc., these rules meet these conditions: neither □ nor ♢ is iterated; none use both □ and ♢. The join of the two systems associated with each of these familiar logics is the full one-step system for that intuitionistic logic. And further “blended” intuitionistic systems arise from joining these systems in various ways. Adding the 0-version of Excluded Middle to their intuitionistic counterparts yields the one-step systems corresponding to the familiar classical logics. Each proof-theoretic system defines a consequence relation in the obvious way. Section 10 examines inclusions between these consequence relations. Section 11 associates each of the above consequence relations with an appropriate class of models, and proves them sound with respect to their appropriate class. This allows proofs of some failures of inclusion between consequence relations. Section 12 proves that the each consequence relation is complete or weakly complete, that relative to its appropriate class of models. The Appendix presents three further results about some of the intuitionistic consequence relations discussed in the body of the paper. For Keywords, see Part 1. (shrink)

Proof uses forcing on perfect trees for 2-quantifier sentences in the language of arithmetic. The result extends to exact pairs for the hyperarithmetic degrees.

This article tackles the sole surviving ancient commentary on what was perhaps the second most important Platonic work, with special interest for the manner in which the ancients tackled the setting of Plato's dialogues, Socratic ignorance, Socratic eros, the central myth-like Palinode, and the question of oral as against written teaching.

Christopher Columbus Langdell has not only damaged the study of law with his three follies: his legal formalism, his redacted appellate case method, and his notion that legal practice taints the professor of law. His three follies have also impaired character development critical for legal actors. This Article focuses on four such critical character traits and virtues impaired by Langdell: (i) imagination, (ii) empathy, (ii) balance, and (iv) integrity. -/- This Article also calls out potential character issues with two professor (...) types inspired by Langdell: (v) the hazing professor who confuses intellectual rigor with intense discomfort and who uses the redacted appellate case method to inflict such discomfort at the expense of better pedagogy, and (vi) the professor without substantial practice experience who is substantially paid to teach what she has never practiced. -/- Agreeing with C.S. Pierce that the best argument is a cable rather than a chain, I end by weaving in a Langdell villanelle. I hope such a cable can help lift Langdell and his follies from legal education and the world. (shrink)