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)

There is no such thing as moral luck or everyone is profoundly mistaken about its nature and a radical rethinking of moral luck is needed. The argument to be developed is not complicated, and relies almost entirely on premises that should seem obviously correct to anyone who follows the moral luck literature. The conclusion, however, is surprising and disturbing. The classic cases of moral luck always involve an agent who lacks control over an event whose occurrence affects her praiseworthiness or (...) blameworthiness. Close examination of what it is to have control or to lack it reveals the logical space for counterexamples that do not fit the pattern constitutive of moral luck, and so unravel the whole. (shrink)

The scant scholarship associated with Newman’s Anglican views about Judaism has focused on his negative rhetoric against Judaism and portrayed him as anti-Semitic. His Anglican writings, however, applied terms associated with Judaism in a typological sense to the political and religious realities of his day, primarily to support his apologetic agenda and to highlight threats to the Church of England. Simultaneously, he stressed the positive characteristics of Judaism, illustrated the continuity between Judaism and Christianity, and pointed out that the religious (...) system of Judaism was divinely inspired and contained worthy examples for Christian living. (shrink)

In recent years, critical discourse concerning the millenarian eschatology of the early Patristic era of Christianity has called into question the common notion that millenarian concepts have been utterly rejected as heretical by the Roman Catholic Church. No Ecumenical Council has ever rejected millenarian eschatology, and papal and juridical statements on the issue have been taken out of context. This essay brings forward, as testing agents, John Henry Newman’s first two notes in Development in order to determine whether Patristic millenarianism, (...) along with a more recently explored version called Eucharistic millenarianism, is a valid example of doctrinal development of an earlier type. Eucharistic millenarianism borrows many aspects from a primitive apostolic source and has been embraced by the Catholic hierarchy, raising the question of how millenarian aspects might legitimately inform contemporary theology. Newman’s theory of the development of doctrine, particularly as seen in his first two notes, is a valuable tool for reevaluating latent concepts that have been unfairly viewed as marginal or even heretical in mainline theological discourse. (shrink)

Atomically precise manufacturing (APM) is the assembly of materials with atomic precision. APM does not currently exist, and may not be feasible, but if it is feasible, then the societal impacts could be dramatic. This paper assesses the net societal impacts of APM across the full range of important APM sectors: general material wealth, environmental issues, military affairs, surveillance, artificial intelligence, and space travel. Positive effects were found for material wealth, the environment, military affairs (specifically nuclear disarmament), and space travel. (...) Negative effects were found for military affairs (specifically rogue actor violence and AI. The net effect for surveillance was ambiguous. The effects for the environment, military affairs, and AI appear to be the largest, with the environment perhaps being the largest of these, suggesting that APM would be net beneficial to society. However, these factors are not well quantified and no definitive conclusion can be made. One conclusion that can be reached is that if APM R&D is pursued, it should go hand-in-hand with effective governance strategies to increase the benefits and reduce the harms. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Plato on Knowledge as a Power1Nicholas D. SmithAt 471C4 in Plato’s Republic, the argument takes a sudden turn when Glaucon becomes impatient with all of the specific prescriptions Socrates has been making, and asks to return to the issue Socrates had earlier set aside—whether or not the city he was describing could ever be brought into being. In response to Glaucon’s impatient question, Socrates articulates his “third wave of (...) paradox” (472ag–7), namely, that the ills of the cities will never be ended until either philosophers become rulers or rulers become philosophers (473c11–d6). Glaucon immediately responds that such a view is likely to be greeted with violence and scorn (473e6–474a4), and so Socrates must hasten to explain his odd claim. His explanation, it turns out, is that true philosophers have an enormous cognitive advantage over non-philosophers—philosophers have and use knowledge (ἐπιστήμη), whereas non-philosophers have and use only opinion (δόξα).2 This distinction, between επιστήμη and δόξα, turns out: to be a distinction between two different cognitive powers (δυνάμεις—477d7–e3). And different powers, Plato clearly tells us, apply to or take as their objects (Plato says they are “ἐπί”) different things (477dl).In this paper, I shall argue that the relationship between the cognitive powers and their various objects has been fundamentally misunderstood, which has led scholars into one or more misinterpretations of important and explicit features of the text. At the heart of these misunderstandings, I claim, is [End Page 145] their shared misconception of the relation between the cognitive power and its objects as interpretable in terms of the relationship between a cognitive stale and what the content of that state is of or about.3 One consequence of the view for which I shall argue is that what has come to be known as the “two-worlds theory”4 of Plato’s epistemology is seriously mistaken, but no less mistaken than the alternatives given by its recent critics. Another consequence that I shall draw from my argument is that Plato should be understood neither as a kind of foundationalist with regard to knowledge and warrant, as some have supposed him to be,5 nor as a coherentist, as others have supposed,6 but, rather, as a kind of causal reliabilist. [End Page 146]1. KNOWLEDGE AS A POWERScholarly interpretations of Plato’s epistemology have routinely sought to understand the relationships between each cognitive power of Republic Book V and the objects of the ἐφ’ ᾦ (“what it is related to”) condition by which it is differentiated from other δυνάμεις as Plato’s way of telling us what each sort of cognition is of or aboul. 7 So, for example, we find Gail Fine using the expressions “belief [δόξα] is set over [Fine’s translation of Plato’s ἐπί] …” and “knowledge is set over …” interchangeably with “belief is of …” or “belief is about…” and “knowledge is of …” or “knowledge is about …”8 Against the “two-worlds theory,” Fine argues that, for Plato, there can be knowledge of sensibles and beliefs about Forms. Accordingly, since she assimilates the power-ἐπί-object set of relations to the cognilion-of/about-object relation, she concludes—in order to account for knowledge of sensibles and beliefs about Forms—that the objects of knowledge and opinion must be propositions. Plato’s claims that knowledge is ἐπί what is, whereas opinion is ἐπί what is and is not, Fine understands as, “One can only know true propositions; one can believe both true and false propositions.”9 We shall see later that this “veridical” understanding of what Plato means to identify as “what is,” and “what is and is not” fails to account for important and explicit elements of Plato’s exposition of the epistemological and metaphysical distinctions he is making. For now, it is enough to note that Fine understands the ἐφ’ᾦ) relation in terms of our cognition-of/about-object relation. One finds the same assimilation made by those who advance existential readings of Plato’s “is” and “is not,”10 as [End Page 147] well as those who have urged that we adopt predicative readings of “is” and “is not.”11But I think there are very serious problems with this assimilation. Plato is very... (shrink)

The replicability of a research claim is often positioned as an important step in establishing the credibility of scientific research. This expectation persists despite ongoing disagreements over how to characterise replication practices in various contexts. Rather than attempt to explain or resolve these disagreements, we propose that there is value in exploring the variable uses of the replicability concept. To this end, we treat the replicability concept as a goal-directed tool for studying scientific practices. This approach extends scholarship on the (...) goal-directed uses of concepts within investigative practices to explore the value of reflexively interrogating those concepts used to study the sciences as practiced. In doing so, we highlight the importance of considering how and when a given concept is an appropriate tool for a given goal when studying scientific practices. For instance, in the case of the replicability concept, our examination suggests that there is value in clarifying how a given characterisation of replicability is appropriate to a given context-specific analytic and/or evaluative goal. In addition, we hope to draw attention to how Metaresearch and HPS contexts provide complementary insights for those seeking to understand when and how replication practices can help in assessing a given research claim. (shrink)

Plato recognizes faction as a serious threat to any political community. The Republic’s proposed solution to faction relies on bringing citizens into a relation of ὁμόνοια. On the dominant line of interpretation, ὁμόνοια is understood along the lines of “explicit agreement” or “consensus.” Commentators have consequently thought that the καλλίπολις becomes resistant to faction when all or most of its members explicitly agree with one another about certain fundamentals of their political association—for example, they agree regarding who should govern in (...) the καλλίπολις.We argue that ὁμόνοια in Plato’s political philosophy has been under-analyzed and misunderstood. We show that, in Alcibiades I, rendering ὁμόνοια simply as agreement results in confusion about how expertise, political friendship, and civic unity are compossible in a well-ordered political community. In our view, Plato refines and adds philosophical depth to the concept of ὁμόνοια in the Republic. We claim that ὁμόνοια is a relation of psychological “like-mindedness” that obtains among members of different occupational classes in a political community. A community is rendered resistant to faction, then, when its members are, in some significant way, psychologically alike. Additionally, while Platonic ὁμόνοια can naturally be expected to result in substantive agreement among citizens, we argue that Platonic ὁμόνοια does not consist solely in agreement. (shrink)

In this paper, we defend Socratic studies as a research programme against several recent attacks, including at least one recently published in Polis. Critics have argued that the study of Socrates, based upon evidence mostly or entirely derived from some set of Plato’s dialogues, is sfounded upon faulty and indefensible historical or hermeneutical technique. We begin by identifying what we believe are the foundational principles of Socratic studies, as the field has been pursued in recent years, and we then show (...) how the research programme that derives from accepting these principles is not defeated by any of the most common recent criticisms of it. Specifically, we argue that challenges to sorting Plato’s dialogues by date, more general challenges to historicist interpretations of Plato’s dialogues, as well as recent literary criticisms of Socratic studies all fail to undermine the research programme. We conclude with some thoughts about how and why Socratic studies has proved itself a valuable and fruitful research programme. (shrink)

An ontology of geographic kinds is designed to yield a better understanding of the structure of the geographic world, and to support the development of geographic information systems that are conceptually sound. This paper first demonstrates that geographical objects and kinds are not just larger versions of the everyday objects and kinds previously studied in cognitive science. Geographic objects are not merely located in space, as are the manipulable objects of table-top space. Rather, they are tied intrinsically to space, and (...) this means that their spatial boundaries are in many cases the most salient features for categorization. The ontology presented here will accordingly be based on topology (the theory of boundary, contact and separation) and on mereology (the theory of extended wholes and parts). Geographic reality comprehends mesoscopic entities, many of which are best viewed as shadows cast onto the spatial plane by human reasoning and language. Because of this, geographic categories are much more likely to show cultural differences in category definitions than are the manipulable objects of table-top space. (shrink)

In the era of “big data,” science is increasingly information driven, and the potential for computers to store, manage, and integrate massive amounts of data has given rise to such new disciplinary fields as biomedical informatics. Applied ontology offers a strategy for the organization of scientific information in computer-tractable form, drawing on concepts not only from computer and information science but also from linguistics, logic, and philosophy. This book provides an introduction to the field of applied ontology that is of (...) particular relevance to biomedicine, covering theoretical components of ontologies, best practices for ontology design, and examples of biomedical ontologies in use. After defining an ontology as a representation of the types of entities in a given domain, the book distinguishes between different kinds of ontologies and taxonomies, and shows how applied ontology draws on more traditional ideas from metaphysics. It presents the core features of the Basic Formal Ontology (BFO), now used by over one hundred ontology projects around the world, and offers examples of domain ontologies that utilize BFO. The book also describes Web Ontology Language (OWL), a common framework for Semantic Web technologies. Throughout, the book provides concrete recommendations for the design and construction of domain ontologies. (shrink)

In the Nintendo game Animal Crossing: New Horizons, players move to an uninhabited island and quickly become instrumental to the naming, aesthetic development, and biodiversity of the island. In some ways, the game can foster a love for and curiosity about nature. In other ways, the game reinforces harmful colonialist values and attitudes that are ultimately an obstacle to conservation in the real world. Here I critique the game values relevant to conservation, both the values that benefit and the values (...) that hinder conservation. I discuss possibilities for a future version of the game that reinforces values better aligned with conservation. (shrink)

This synthesis of 5 prominent conflict management paradigms uses power differential as the single most contributing variable to their process and outcome of conflict. Efforts of scholars to integrate or synthesize conflict paradigms have been unsuccessful or clumsy by the scholars’ own assessments. The 5 selected paradigms represent an interdisciplinary set of normative and descriptive paradigms from different social contexts and intellectual frameworks. The 5 share the common traits of rival goals, three levels of socially constructed power differential, and outcomes (...) relative to the total value of the rival goal. An inverse relationship between power differential and the total value of conflict outcomes is supported by all 5 paradigms and empirical data. Explanatory metatheory is the methodology used for synthesis. An increase in power differential results in a decrease in total value of the rival goal. Power differential is constructed using Max Weber’s ideal-type method. The power differentials are abstracted from the paradigms themselves. Empirical work form secondary sources and case studies complete the analysis. (shrink)

The notion of function is indispensable to our understanding of distinctions such as that between being broken and being in working order (for artifacts) and between being diseased and being healthy (for organisms). A clear account of the ontology of functions and functioning is thus an important desideratum for any top-level ontology intended for application to domains such as engineering or medicine. The benefit of using top-level ontologies in applied ontology can only be realized when each of the categories identified (...) and defined by a top-level ontology is integrated with the others in a coherent fashion. Basic Formal Ontology (BFO) has from the beginning included function as one of its categories, exploiting a version of the etiological account of function that is framed at a level of generality sufficient to accommodate both biological and artifactual functions. This account has been subjected to a series of criticisms and refinements. We here articulate BFO’s account of function, provide some reasons for favoring it over competing views, and defend it against objections. (shrink)

It has been argued that Plato sought to make his rulers invulnerable to any kind of wrongdoing. In this paper we argue that this (humanly impossible) claim misunderstand the ways in which Plato shapes his state precisely in order to make the rulers safe from what could corrupt them.

In this paper we argue that Socrates is a cognitivist about emotions, but then ask how the beliefs that constitute emotions can come into being, and why those beliefs seem more resistant to change through rational persuasion than other beliefs.

In the era of “big data,” science is increasingly information driven, and the potential for computers to store, manage, and integrate massive amounts of data has given rise to such new disciplinary fields as biomedical informatics. Applied ontology offers a strategy for the organization of scientific information in computer-tractable form, drawing on concepts not only from computer and information science but also from linguistics, logic, and philosophy. This book provides an introduction to the field of applied ontology that is of (...) particular relevance to biomedicine, covering theoretical components of ontologies, best practices for ontology design, and examples of biomedical ontologies in use. After defining an ontology as a representation of the types of entities in a given domain, the book distinguishes between different kinds of ontologies and taxonomies, and shows how applied ontology draws on more traditional ideas from metaphysics. It presents the core features of the Basic Formal Ontology (BFO), now used by over one hundred ontology projects around the world, and offers examples of domain ontologies that utilize BFO. The book also describes Web Ontology Language (OWL), a common framework for Semantic Web technologies. Throughout, the book provides concrete recommendations for the design and construction of domain ontologies. (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.

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

Aworkshop was held August 26–28, 2015, by the Earth- Life Science Institute (ELSI) Origins Network (EON, see Appendix I) at the Tokyo Institute of Technology. This meeting gathered a diverse group of around 40 scholars researching the origins of life (OoL) from various perspectives with the intent to find common ground, identify key questions and investigations for progress, and guide EON by suggesting a roadmap of activities. Specific challenges that the attendees were encouraged to address included the following: What key (...) questions, ideas, and investigations should the OoL research community address in the near and long term? How can this community better organize itself and prioritize its efforts? What roles can particular subfields play, and what can ELSI and EON do to facilitate research progress? (See also Appendix II.) The present document is a product of that workshop; a white paper that serves as a record of the discussion that took place and a guide and stimulus to the solution of the most urgent and important issues in the study of the OoL. This paper is not intended to be comprehensive or a balanced representation of the opinions of the entire OoL research community. It is intended to present a number of important position statements that contain many aspirational goals and suggestions as to how progress can be made in understanding the OoL. The key role played in the field by current societies and recurring meetings over the past many decades is fully acknowledged, including the International Society for the Study of the Origin of Life (ISSOL) and its official journal Origins of Life and Evolution of Biospheres, as well as the International Society for Artificial Life (ISAL). (shrink)

J. M. E. McTaggart’s anti-passage argument (the argument that time is “unreal) has misled philosophers of time for almost a century. The present paper shows that the clearest formulation of this argument, that of D. H. Mellor in Real Time II, is unsound when its premises are interpreted so that it is valid and invalid when it so interpreted that it is sound). This argument need mislead us no longer. -/- The crucial item in the interpretation of the premises is (...) the copula ‘is’, as in ‘E is past’. The copula may be either tensed or tenseless. While this ambiguity of the copula has been noted before, its implications for McTaggart’s argument had not been adequately exploited. This paper does that job. (shrink)

Functional diversity holds the promise of understanding ecosystems in ways unattainable by taxonomic diversity studies. Underlying this promise is the intuition that investigating the diversity of what organisms actually do—i.e. their functional traits—within ecosystems will generate more reliable insights into the ways these ecosystems behave, compared to considering only species diversity. But this promise also rests on several conceptual and methodological—i.e. epistemic—assumptions that cut across various theories and domains of ecology. These assumptions should be clearly addressed, notably for the sake (...) of an effective comparison and integration across domains, and for assessing whether or not to use functional diversity approaches for developing ecological management strategies. The objective of this contribution is to identify and critically analyze the most salient of these assumptions. To this aim, we provide an “epistemic roadmap” that pinpoints these assumptions along a set of historical, conceptual, empirical, theoretical, and normative dimensions. (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)

Current COVID-19 pandemic and previous SARS/MERS outbreaks have caused a series of major crises to global public health. We must integrate the large and exponentially growing amount of heterogeneous coronavirus data to better understand coronaviruses and associated disease mechanisms, in the interest of developing effective and safe vaccines and drugs. Ontologies have emerged to play an important role in standard knowledge and data representation, integration, sharing, and analysis. We have initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO). (...) As an Open Biomedical Ontology (OBO) library ontology, CIDO is an open source and interoperable with other existing OBO ontologies. In this article, the general architecture and the design patterns of the CIDO are introduced, CIDO representation of coronaviruses, phenotypes, anti-coronavirus drugs and medical devices (e.g. ventilators) are illustrated, and an application of CIDO implemented to identify repurposable drug candidates for effective and safe COVID-19 treatment is presented. (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)

Safe-by-Design (SBD) frameworks for the development of emerging technologies have become an ever more popular means by which scholars argue that transformative emerging technologies can safely incorporate human values. One such popular SBD methodology is called Value Sensitive Design (VSD). A central tenet of this design methodology is to investigate stakeholder values and design those values into technologies during early stage research and development (R&D). To accomplish this, the VSD framework mandates that designers consult the philosophical and ethical literature to (...) best determine how to weigh moral trade-offs. However, the VSD framework also concedes the universalism of moral values, particularly the values of freedom, autonomy, equality trust and privacy justice. This paper argues that the VSD methodology, particularly applied to nano-bio-info-cogno (NBIC) technologies, has an insufficient grounding for the determination of moral values. As such, an exploration of the value-investigations of VSD are deconstructed to illustrate both its strengths and weaknesses. This paper also provides possible modalities for the strengthening of the VSD methodology, particularly through the application of moral imagination and how moral imagination exceed the boundaries of moral intuitions in the development of novel technologies. (shrink)

The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in (...) other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors’ rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs. (shrink)

Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized terminology (...) for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (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 Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) (...) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer’s disease, multiple sclerosis, and stroke. (shrink)

We have begun work on two separate but related ontologies for the study of neurological diseases. The first, the Neurological Disease Ontology (ND), is intended to provide a set of controlled, logically connected classes to describe the range of neurological diseases and their associated signs and symptoms, assessments, diagnoses, and interventions that are encountered in the course of clinical practice. ND is built as an extension of the Ontology for General Medical Sciences — a high-level candidate OBO Foundry ontology that (...) provides a set of general classes that can be used to describe general aspects of medical science. ND is being built with classes utilizing both textual and axiomatized definitions that describe and formalize the relations between instances of other classes within the ontology itself as well as to external ontologies such as the Gene Ontology, Cell Ontology, Protein Ontology, and Chemical Entities of Biological Interest. In addition, references to similar or associated terms in external ontologies, vocabularies and terminologies are included when possible. Initial work on ND is focused on the areas of Alzheimer’s and other diseases associated with dementia, multiple sclerosis, and stroke and cerebrovascular disease. Extensions to additional groups of neurological diseases are planned. The second ontology, the Neuro-Psychological Testing Ontology (NPT), is intended to provide a set of classes for the annotation of neuropsychological testing data. The intention of this ontology is to allow for the integration of results from a variety of neuropsychological tests that assay similar measures of cognitive functioning. Neuro-psychological testing is an important component in developing the clinical picture used in the diagnosis of patients with a range of neurological diseases, such as Alzheimer’s disease and multiple sclerosis, and following stroke or traumatic brain injury. NPT is being developed as an extension to the Ontology for Biomedical Investigations. (shrink)

The project of a naive physics has been the subject of attention in recent years above all in the artificial intelligence field, in connection with work on common-sense reasoning, perceptual representation and robotics. The idea of a theory of the common-sense world is however much older than this, having its roots not least in the work of phenomenologists and Gestalt psychologists such as Kohler, Husserl, Schapp and Gibson. This paper seeks to show how contemporary naive physicists can profit from a (...) knowledge of these historical roots of their discipline, which are shown to imply above all a critique of the set-theory-based models of reality typically presupposed by contemporary work in common-sense ontology. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (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)

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 Plant Ontology (PO) (http://www.plantontology.org) (Jaiswal et al., 2005; Avraham et al., 2008) was designed to facilitate cross-database querying and to foster consistent use of plant-specific terminology in annotation. As new data are generated from the ever-expanding list of plant genome projects, the need for a consistent, cross-taxon vocabulary has grown. To meet this need, the PO is being expanded to represent all plants. This is the first ontology designed to encompass anatomical structures as well as growth and developmental stages (...) across such a broad taxonomic range. While other ontologies such as the Gene Ontology (GO) (The Gene Ontology Consortium, 2010) or Cell Type Ontology (CL) (Bard et al., 2005) cover all living organisms, they are confined to structures at the cellular level and below. The diversity of growth forms and life histories within plants presents a challenge, but also provides unique opportunities to study developmental and evolutionary homology across organisms. (shrink)

Safe-by-Design (SBD) frameworks for the development of emerging technologies have become an ever more popular means by which scholars argue that transformative emerging technologies can safely incorporate human values. One such popular SBD methodology is called Value Sensitive Design (VSD). A central tenet of this design methodology is to investigate stakeholder values and design those values into technologies during early stage research and development (R&D). To accomplish this, the VSD framework mandates that designers consult the philosophical and ethical literature to (...) best determine how to weigh moral trade-offs. However, the VSD framework also concedes the universalism of moral values, particularly the values of freedom, autonomy, equality trust and privacy justice. This paper argues that the VSD methodology, particularly applied to nano-bio-info-cogno (NBIC) technologies, has an insufficient grounding for the determination of moral values. As such, an exploration of the value-investigations of VSD are deconstructed to illustrate both its strengths and weaknesses. This paper also provides possible modalities for the strengthening of the VSD methodology, particularly through the application of moral imagination and how moral imagination exceed the boundaries of moral intuitions in the development of novel technologies. (shrink)

In this book review, I discuss Smith’s new interpretation of Socrates' epistemology of virtue, according to which (a) Socratic virtue knowledge is craft knowledge (knowing how to live well), and such knowledge comes in degrees; and (b) Socrates has a certain degree of virtue knowledge, and one does not have to be an inerrant expert to have any virtue knowledge at all. I argue that Smith succeeds in presenting Socratic philosophy in a new light, while also pointing to (...) remaining questions about his account of virtue—specifically, about what exactly the craft of virtue is and how we can practice it and thereby improve ourselves. (shrink)

There are two primary camps in which nanotechnology today can be categorized normal nanotechnology and speculative nanotechnology. The birth of nanotechnology proper was conceived through discourses of speculative nanotechnology. However, current nanotech-nology research has detracted from its speculative promises in favour of more attainable material products. Nonetheless, normal nanotechnology has leveraged the popular support and consequential funding it needs to conduct research and development (R&D) as a result of popular conceptions of speculative nanotechnology and its promises. Similarly, the scholarly literature (...) has shifted its focus away from speculative nanofutures towards normal nanotech-nology R&D. This paper shows that there is an incongruence between the representation of nanotechnology in the media, scholarly journals and industry. (shrink)

In Christ Brings All Newness: Essays, Reviews, and Reflections, Robert P. Imbelli, a theologian with a storied vocation as a priest of the Archdiocese of New York, offers a rich theological corpus explicitly grounded in Vatican II’s transformative vision. A scholar who bore witness to the unfolding of the council while studying in Rome, Imbelli carries the torch of its teachings through over five decades of preaching and teaching. With a Ph.D. in theology from Yale University, he has cultivated a (...) nuanced and sober understanding of the Catholic imagination, reflected in his previous award-winning work, Rekindling the Christic Imagination. In this current volume, Imbelli delves into the inexhaustible newness of Jesus Christ, examining how this novum has been, and ought to be, the pulsating heart of Catholic thought and praxis. The collection is poised as a bridge spanning scholarly exegesis and pastoral ministry, calling believers to re-encounter the transformative presence of Christ in an era where such a center often seems perilously close to erosion. (shrink)

The most obvious varieties of mental phenomena directed to non- existent objects occur in our experiences of works of art. The task of applying the Meinongian ontology of the non-existent to the working out of a theory of aesthetic phenomena was however carried out not by Meinong by his disciple Stephan Witasek in his Grundzüge der allgemeinen Ästhetik of 1904. Witasek shows in detail how our feelings undergo certain sorts of structural modifications when they are directed towards what does not (...) exist. He draws a distinction between genuine mental phenomena and what he calls `phantasy-material', asserting that `the job of the aesthetic object, whether it is a work of art or a product of nature, is to excite and support the actualisation of phantasy-material in the experiencing subject'. We might think of such phantasy-material as a matter of Ersatz-emotions or emotional `slop'. We could then see Witasek's aesthetics as an elaborate taxonomy of the various different sorts of Ersatz-emotions which the subject allows to be stimulated within himself in his intercourse with works of art, and see works of art themselves as machines for the production of ever more subtle varieties of such phantasy-material in the perceiving subject. (shrink)

Logique et existenceDeleuze à propos des « conditions du réel »Pour Deleuze, l’un des problèmes fondamentaux d’une théorie de la pensée est de savoir comment la pensée peut quitter la sphère du possible pour penser le réel, c’est-àdire pour penser l’existence elle-même. La position du réel semble être hors du concept. Des pré-kantiens comme Leibniz approchaient ce problème par le biais de la distinction entre vérités d’essence et vérités d’existence, alors que des post-kantiens comme Maimon l’approchaient par la distinction entre (...) les conditions de l’expérience possible et celles de l’expérience réelle. La logique classique définit la sphère du possible par trois principes logiques – l’identité, la non-contradiction et le tiers-exclu – et la présente étude examine les trois grandes trajectoires qui, dans cette histoire de la philosophie, ont tenté d’utiliser l’un de ces trois principes classiques pour pénétrer l’existence ellemême : 1) Leibniz (et les pré-kantiens) cherchait à étendre le principe de d’identité àl’existence entière ; 2) Hegel (et les post-kantiens) cherchait à étendre le principe de non-contradiction à la totalité de l’expérience ; et 3) le groupe des penseurs appelés de manière assez large « existentialistes » cherchait à étendre le principe du tiers-exclu à la totalité de l’existence. La conclusion examine les raisons pour lesquelles Deleuze a été fasciné par chacune de ces tentatives philosophiques pour « penser l’existence », tout en pensant néanmoins qu’elles ont toutes échoué ; et pourquoi aussi il a fini par développer sa propre réponse au problème en faisant appel à un principe de différence.Logica e EsistenzaLe ‘Condizioni del reale’ in DeleuzePer Deleuze, uno dei problemi fondamentali per una teoria del pensiero è: come può il pensiero abbandonare la sfera del possibile per pensare il reale, ossia, pensare l’esistenza stessa? La posizione del reale sembra essere fuori dal concetto. Prekantiani come Leibniz affrontano questo problema in termini di distinzione fra verità dell’essenza e verità dell’esistenza, mentre post-kantiani come Maimon affrontano il problema in termini di distinzione fra condizioni dell’esperienza possibile e condizioni dell’esperienza reale. La logica classica ha definito la sfera del possibile secondo tre principi logici – identità, non-contraddizione, terzo escluso – e questo saggio analizza tre grandi ‘parabole’ della storia della filosofia che hanno tentato di usare uno di questi tre principi della logica per penetrare l’esistenza stessa: (1) Leibniz (e i pre-kantiani) hanno tentato di estendere il principio di identità a tutta l’esistenza; (2) Hegel (ei post-kantiani) hanno tentato di estendere il principio di non-contraddizione a tutta l’esistenza; (3) il gruppo di pensatori (solo approssimativamente legati fra loro) chiamati “esistenzialisti” ha tentato di estendere il principio del terzo escluso all’esistenza. La conclusione analizza sia le ragioni per le quali Deleuze era affascinato da ciascuno di questi tentativi filosofici di “pensare l’esistenza” nonostante fosse convinto che essi avessero fallito, sia i motivi per cui egli in conclusione traccia la propria risposta al problema facendo appello al principio della differenza. (shrink)

Le présent article est une tentative nouvelle d’articuler le rôle d’une théorie des vérifacteurs. Nous soutenons que la théorie de la vérifaction constitue une pierre angulaire dans une bonne méthodologie en métaphysique, mais que l’amalgame entre la théorie de la vérifaction et la théorie de la vérité a été responsable de certains excès associés aux approches vérifactionnistes dans la littérature récente. Nous montrons que la théorie de la vérifaction conserve son attrait comme instrument d’investigation métaphysique, et ce, malgré notre accord (...) avec les doctrines déflationnistes telles que celles défendues par Ayer, Quine, Field et Horwich (ou, du moins, malgré notre neutralité à leur égard). Nous soutenons en outre que les intuitions sous-jacentes à la théorie de la vérifaction s’éclairent quand nous les dissocions d’une théorie de la vérité et, par-dessus tout, de la tentative de fournir une définition de la vérité. (shrink)