COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved (...) in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

Law being a derivative feature of reality, it exists in virtue of more fundamental things, upon which it depends. This raises the question of what is the relation of dependence that holds between law and its more basic determinants. The primary aim of this paper is to argue that grounding is that relation. We first make a positive case for this claim, and then we defend it from the potential objection that the relevant relation is rather rational determination (Greenberg 2004, (...) 2006). Against this challenge, we argue that the apparent objection is really no objection, for on its best understanding, rational determination turns out to actually be grounding. Finally, we clarify the framework for theories on law-determination that results from embracing our view; by way of illustration, we offer a ground-theoretic interpretation of Hartian positivism, and show how it can defuse an influential challenge to simple positivist accounts of law. (shrink)

A new strategy in philosophy of law appeals to explanatory gap arguments to attack legal positivism. We argue that the strategy faces a dilemma, which derives from there being two available readings of the constraint it places on legal grounding. To this end, we elaborate the most promising ways of spelling out the epistemic constraints governing law-determination, and show that each of the arguments based on them has problems. Throughout the paper, we evaluate a number of explanatory requirements, ultimately with (...) a view to shedding light on the explanatory nature of both grounding in general, and legal grounding in particular. (shrink)

This work has been selected by scholars as being culturally important and is part of the knowledge base of civilization as we know it. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be (...) preserved, reproduced, and made generally available to the public. To ensure a quality reading experience, this work has been proofread and republished using a format that seamlessly blends the original graphical elements with text in an easy-to-read typeface. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

This paper examines people's reasoning about identity continuity and its relation to previous research on how people value one-of-a-kind artifacts, such as artwork. We propose that judgments about the continuity of artworks are related to judgments about the continuity of individual persons because art objects are seen as physical extensions of their creators. We report a reanalysis of previous data and the results of two new empirical studies that test this hypothesis. The first study demonstrates that the mere categorization of (...) an object as “art” versus “a tool” changes people's intuitions about the persistence of those objects over time. In a second study, we examine some conditions that may lead artworks to be thought of as different from other artifacts. These observations inform both current understanding of what makes some objects one-of-a-kind as well as broader questions regarding how people intuitively think about the persistence of human agents. (shrink)

The concept of authenticity plays an important role in how people reason about objects, other people, and themselves. However, despite a great deal of academic interest in this concept, to date, the precise meaning of the term, authenticity, has remained somewhat elusive. This paper reviews the various definitions of authenticity that have been proposed in the literature and identifies areas of convergence. We then outline a novel framework that organizes the existing definitions of authenticity along two key dimensions: describing the (...) type of entity that is evaluated and describing the source of information that is consulted. We argue that this convergence across a number of papers, and more importantly, across a number of domains, reflects significant progress in articulating the meaning of authenticity. We conclude by suggesting new avenues for research in this area, with particular attention toward psychological process. (shrink)

BackgroundOne of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it.MethodsWe conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the (...) United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable.ResultsAll four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL.ConclusionBecause of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings. (shrink)

First Published in 1999. Routledge is an imprint of Taylor & Francis, an informa company.

Modern Jewish Theology is the first comprehensive collection of Jewish theological ideas from the pathbreaking nineteenth and early twentieth centuries, featuring selections from more than thirty of the most influential modern Jewish thinkers of the era.

The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, as these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focussed on marker development and cellular stress as well as on diseases, in particular on diseases of kidney (...) and skin. (shrink)

A miracle is defined as a violation of or intercession in the laws of nature. Some recent reports of UFO phenomena are such that UFOs may satisfy that definition. In this paper, we ask how Hume’s famous argument in “Of Miracles” relates to UFOs. We argue that his critique fails and that some well corroborated UFO reports are such that they justify a belief in miracles (qua violations of laws of nature).

Although the referents of the term social capital merit sustained inquiry, the term impedes understanding because of the historical association of the word capital with economic discourse. As a result of this association, applying the term social capital to civic engagement blurs crucial analytic distinctions. Moreover, there are important ideological consequences to considering things such as bowling leagues to be a form of capital and urging citizens to become social capitalists. The term social capacity, the authors argue, provides the same (...) heuristic benefits as the term social capital without extending illusory promises of theoretical parsimony with the financial/human/social capital trinity. (shrink)

Methuselah, it is said, lived 969 years. His state of health at death is not revealed. It can only be surmised that he was surely not robust and, no doubt, was subject to all of the infirmities of old age and the tragic indignities associated with senility.Jonathan Swift captured well the “curse” of immortality when, in Gulliver's Travels, he created a group of individuals, the Struldbrugs, who, when encountered, dulled what had heretofore been an appetite for perpetual life. The Struldbrugs (...) were allowed to be born totally exempt from the “calamity of human Nature,” in that their minds were free “and disingaged, without the Weight and De pression of Spirits caused by the continued Apprehension of Death.” They were thus condemned “to a perpetual continuance in the World.” In his travels, Gulliver found some Struldbrugs well over 1,000 years old. (shrink)

Not everyone finds a in suffering. Indeed, even those who do subscribe to this interpretation recognize the responsibility of each individual to show not only sensitivity and compassion but render assistance to those in distress. Pharmacologic hypnosis, morphine intoxication, and terminal sedation provide their own type of medical to the terminally ill patient suffering unremitting pain. More and more states are enacting legislation that recognizes this need of the dying to receive relief through regulated administration of controlled substances. Wider legislative (...) recognition of this need would go far toward allowing physicians, in the exercise of their reasonable medical judgment, to administer a range of narcotics and barbiturates to the terminally ill without fear of legal sanctions. Sadly, social attitudes and governmental concerns about the spread of drug addiction provide an undeniable policy nexus that impedes unduly a rational approach or exception for the treatment of pain experienced by the dying. (shrink)

Reason and Value collects fifteen brand-new papers by leading contemporary philosophers on themes from the moral philosophy of Joseph Raz. The subtlety and power of Raz's reflections on ethical topics - including especially his explorations of the connections between practical reason and the theory of value - make his writings a fertile source for anyone working in this area. The volume honours Raz's accomplishments in the area of ethical theorizing, and will contribute to an enhanced appreciation of the significance of (...) his work for the subject. (shrink)

In this volume a team of distinguished contributors examine all the main aspects of Newton s thought, including not only his approach to space, time, mechanics, ...