Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it is (...) associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. (shrink)

Recombinant adeno‐associated viruses (rAAVs) are promising vectors for the delivery of various genetic constructs into eukaryotic cells. rAAVs have a number of properties that make it possible to successfully use them both in vitro and in vivo. Purification and concentration of rAAV vectors are critical for achieving high viral titer, stability, efficiency, and purity. This review systematically analyses all available purification approaches. The purification methods described in this work differ substantially from each other in mechanisms, efficiency, labor time, and cost. (...) Researchers have to choose a purification algorithm depending on the purpose of their work. We strive to simplify the choice of the necessary and sufficient technique based on the experimental needs and available resources of the laboratory. (shrink)

A supplemental document for "Metalinguistic Gradability".

Two sources of possible disagreement in bioethics may be associated with pessimism about what bioethics can achieve. First, pluralism implies that bioethics engages with interlocutors who hold divergent moral beliefs. Pessimists might believe that these disagreements significantly limit the extent to which bioethics can provide normatively robust guidance in relevant areas. Second, the interdisciplinary nature of bioethics suggests that interlocutors may hold divergent views on the nature of bioethics itself—particularly its practicality. Pessimists may suppose that interdisciplinary disagreements could frustrate the (...) goals of bioethics. In this article, I explore how wonder may alleviate the concerns of the first group of pessimists regarding problems associated with pluralism, provided that we are willing to accept some interdisciplinary frustrations. Then, I invite readers of this issue of The Journal of Medicine & Philosophy to test these intuitions by considering the role of wonder in these articles. (shrink)

In this paper we discuss how Causal Decision Theory should be modified to handle a class of problematic cases involving deterministic laws. Causal Decision Theory, as it stands, is problematically biased against your endorsing deterministic propositions (for example it tells you to deny Newtonian physics, regardless of how confident you are of its truth). Our response is that this is not a problem for Causal Decision Theory per se, but arises because of the standard method for assessing the truth of (...) certain counterfactuals. The truth of deterministic laws is `modally fragile' on the standard semantics for counterfactuals: if determinism is true and you were to do otherwise, the laws would be different. We provide two ways of avoiding this problem: 1) supplement the standard semantics for counterfactuals with impossible worlds, or 2) introduce rigid designators into the description of problematic decision situations. We argue that both of these approaches are well-motivated and can be readily incorporated into Lewisian Causal Decision Theory. (shrink)

Multiple states are at risk of becoming uninhabitable due to climate change, forcing their populations to flee. While the 1951 Refugee Convention provides the gold standard of international protection, it is only applied to a limited subset of people fleeing their countries, those who suffer persecution, which most people fleeing climate change cannot establish. While many journalists and non-lawyers freely use the term “climate refugees,” governments, and courts, as well as UNHCR and many refugee experts, have excluded most climate refugees (...) from the Convention as a matter of legal interpretation. In our 2015 paper, “Unable to Return in the 1951 Refugee Convention: Stateless Refugees and Climate Change”, we sought to reopen the debate on “climate refugees” by arguing that some climate refugees qualify under the 1951 Convention as it is currently written (even if they are not persecuted): those who are stateless and are unable to return to their country of origin because climate change has rendered it uninhabitable. Our interpretation, however, has been rejected by Goodwin-Gill and McAdam (2021) and by Foster and Lambert (2019), which explicitly responds to our paper. Here, we address and respond to their arguments, and develop a new supplementary one, drawing on the principle of systemic integration, as enshrined in Article 31(3)(c) of the Vienna Convention on the Law of Treaties. (shrink)

In the paper, a detailed analysis of some new logical aspects of Cantor’s diagonal proof of the uncountability of continuum is presented. For the first time, strict formal, axiomatic, and algorithmic definitions of the notions of potential and actual infinities are presented. It is shown that the actualization of infinite sets and sequences used in Cantor’s proof is a necessary, but hidden, condition of the proof. The explication of the necessary condition and its factual usage within the framework of Cantor’s (...) proof makes, Cantor’s proof invalid. It’s shown that traditional Cantor’s proof has a second necessary, but hidden as well, condition which is teleological by its nature, i.e., is not mathematical. The explication of the second necessary condition makes Cantor’s statement on the uncountability of continuum unprovable from the point of view of classical logic.One of the most dramatic facts in history of science is connected just with the notion of actual infinity and consists in the following. On the one hand, Aristotle, Berkeley, Locke, Descartes, Spinoza, Gauss, Kant, Cauchy, Kronecker, Hermite, Poincaré, Bair, Borel, Brouwer, Quine, Wittgenstein, Weyl, Luzin, and a lot of other outstanding creators of classical logic and classical mathematics, during millenniums, stated categorically and insistently warned about that the actual infinity is a self-contradictory notion and its usage in mathematics is inadmissible (e.g., according to Poincare, “There is no actual infinity. - Cantorians forgot that and fell into contradictions. Later generations will regard Mengenlehre (set theory) as a disease from which one has recovered”). On the other hand, a lot of outstanding scientists of the XX c.c., such as Hilbert, Church, Turing, Gödel, etc., and modern axiomatic set theory as a whole ignored this (intuitive though) opinion of genii and accepted Cantor’s “transfinite paradise”, based on the actual infinity. In the paper some logical, philosophical, and psychological aspects of this historical “favorable opposition” are analyzed, and the fact that the scientific intuition of genii has won the historical battle against the mytho-’logic’ of Cantor’s transfinite ‘paradise’ is explained and logically justified. (shrink)

In the paper, a detailed analysis of some new logical aspects of Cantor’s diagonal proof of the uncountability of continuum is presented. For the first time, strict formal, axiomatic, and algorithmic definitions of the notions of potential and actual infinities are presented. It is shown that the actualization of infinite sets and sequences used in Cantor’s proof is a necessary, but hidden, condition of the proof. The explication of the necessary condition and its factual usage within the framework of Cantor’s (...) proof makes, Cantor’s proof invalid. It’s shown that traditional Cantor’s proof has a second necessary, but hidden as well, condition which is teleological by its nature, i.e., is not mathematical. The explication of the second necessary condition makes Cantor’s statement on the uncountability of continuum unprovable from the point of view of classical logic.One of the most dramatic facts in history of science is connected just with the notion of actual infinity and consists in the following. On the one hand, Aristotle, Berkeley, Locke, Descartes, Spinoza, Gauss, Kant, Cauchy, Kronecker, Hermite, Poincaré, Bair, Borel, Brouwer, Quine, Wittgenstein, Weyl, Luzin, and a lot of other outstanding creators of classical logic and classical mathematics, during millenniums, stated categorically and insistently warned about that the actual infinity is a self-contradictory notion and its usage in mathematics is inadmissible (e.g., according to Poincare, “There is no actual infinity. - Cantorians forgot that and fell into contradictions. Later generations will regard Mengenlehre (set theory) as a disease from which one has recovered”). On the other hand, a lot of outstanding scientists of the XX c.c., such as Hilbert, Church, Turing, Gödel, etc., and modern axiomatic set theory as a whole ignored this (intuitive though) opinion of genii and accepted Cantor’s “transfinite paradise”, based on the actual infinity. In the paper some logical, philosophical, and psychological aspects of this historical “favorable opposition” are analyzed, and the fact that the scientific intuition of genii has won the historical battle against the mytho-’logic’ of Cantor’s transfinite ‘paradise’ is explained and logically justified. (shrink)

Mental causation is notoriously threatened by the causal exclusion argument. A prominent strategy to save mental causation from causal exclusion consists in subscribing to an interventionist account of causation. This move has, however, recently been challenged by several authors. In this paper, we do two things: We (i) develop what we consider to be the strongest version of the interventionist causal exclusion argument currently on the market and (ii) propose a new way how it can in principle be overcome. In (...) particular, we propose to replace strict supervenience in the assumption that the mental supervenes on the physical by probabilistic supervenience and show how this move has the potential to license the inference to mental causation. Finally, we argue that probabilistic supervenience captures some of the most important intuitions that strict supervenience captures and discuss possible objections to weakening strict supervenience in the way we suggest. (shrink)

A new speculative ontology of aesthetics. In Aesthesis and Perceptronium, Alexander Wilson presents a theory of materialist and posthumanist aesthetics founded on an original speculative ontology that addresses the interconnections of experience, cognition, organism, and matter. Entering the active fields of contemporary thought known as the new materialisms and realisms, Wilson argues for a rigorous redefining of the criteria that allow us to discriminate between those materials and objects where aesthesis (perception, cognition) takes place and those where it doesn't. (...) Aesthesis and Perceptronium negotiates between indiscriminately pluralist views that attribute mentation to all things and eliminative views that deny the existence of mentation even in humans. By recasting aesthetic questions within the framework of "epistemaesthetics," which considers cognition and aesthetics as belonging to a single category that can neither be fully disentangled nor fully reduced to either of its terms, Wilson forges a theory of nonhuman experience that avoids this untenable dilemma. Through a novel consideration of the evolutionary origins of cognition and its extension in technological developments, the investigation culminates in a rigorous reevaluation of the status of matter, information, computation, causality, and time in terms of their logical and causal engagement with the activities of human and nonhuman agents. (shrink)

This paper commences by making a case for a naturalized approach to knowledge‐first epistemology. On this basis it then goes on to describe and defend a naturalized, functionalist account of group knowledge. It then contrasts this with Jennifer Lackey's (2021) account of the epistemological status of groups.

For a novice this book is a mathematically-oriented introduction to modal logic, the discipline within mathematical logic studying mathematical models of reasoning which involve various kinds of modal operators. It starts with very fundamental concepts and gradually proceeds to the front line of current research, introducing in full details the modern semantic and algebraic apparatus and covering practically all classical results in the field. It contains both numerous exercises and open problems, and presupposes only minimal knowledge in mathematics. A specialist (...) can use the book as a source of references. Results and methods of many directions in propositional modal logic, from completeness and duality to algorithmic problems, are collected and systematically presented in one volume. (shrink)

Kant and Fichte developed the concept of a worldview as a way of reflecting on experience as a whole. But what does it mean to form a worldview? And what role did it play in the German Idealist tradition? This paper seeks to answer these questions through a detailed analysis of the form of a philosophical worldview and its historical portent, both of which remain unexplored in the literature. The dearth of attention is partially to blame on Kant’s desultory development (...) of it, as well as its place in Fichte’s understudied lectures on religion. In this paper, I first reconstruct Kant’s conception as the starting point and then trace it to Fichte who went on to evolve it further. Fichte endorses the basic conceptual shape pioneered by Kant, namely, a reflective process of positing an idea and then checking the coherence of necessary judgments relative to it. However, Fichte came to realize that its philosophical function needed expanding. Beyond recognizing the possibility for alternative worldviews, Fichte further fleshed out how worldview creation could lead to human flourishing. The common feature between both thinkers is that the formation of a worldview aims to turn philosophy into a life-orienting exercise. (shrink)

Kant’s accounts of the Highest Good and the moral argument for God and immortality are central features of his philosophy. But both involve lingering puzzles. In this entry, we first explore what the Highest Good is for Kant and the role it plays in a complete account of ethical life. We then focus on whether the Highest Good involves individuals only, or whether it also connects with Kant’s doctrines about the moral progress of the species. In conclusion, we look into (...) three ways of articulating the moral argument for God and immorality that take our commitment to the Highest Good as their point of departure. (shrink)

The familiar Vendler-Kenny scheme of verb-types, viz., performances (further differentiated by Vedler into accomplishments and achievements), activities, and states, is too narrow in two important respects. First, it is narrow linguistically. It fails to take into account the phenomenon of verb aspect. The trichotomy is not one of verbs as lexical types but of predications. Second, the trichotomy is narrow ontologically. It is a specification in the context of human agency of the more fundamental, topic-neutral trichotomy, event-process-state.The central component in (...) this ontological trichotomy, event, can be sharply differentiated from its two flanking components by adapting a suggestion by Geoffrey N. Leech and others that the contrast between perfective and imperfective aspect in verbs corresponds to the count/mass distinction in the domain of nouns. With the help of two distinctions, of cardinal count adverbials versus frequency adverbials, and of occurrence versus associated occasion, two interrelated criteria for event predication are developed. Accordingly, Mary capsized the boat is an event predication because (a) it is equivalent to There was at least one capsizing of the boat by Mary, or (b) because it admits cardinal count adverbials, e.g., at least once, twice, three times. Ontologically speaking, events are defined as those occurrences that are inherently countable. (shrink)

Analyzes the poem "On Nature" by Parmenides, arguing that is actually a philosophical argument disguised as Homer-like mythological journey. Original.

There is an underlying assumption in the social sciences that consciousness and social life are ultimately classical physical/material phenomena. In this ground-breaking book, Alexander Wendt challenges this assumption by proposing that consciousness is, in fact, a macroscopic quantum mechanical phenomenon. In the first half of the book, Wendt justifies the insertion of quantum theory into social scientific debates, introduces social scientists to quantum theory and the philosophical controversy about its interpretation, and then defends the quantum consciousness hypothesis against the (...) orthodox, classical approach to the mind-body problem. In the second half, he develops the implications of this metaphysical perspective for the nature of language and the agent-structure problem in social ontology. Wendt's argument is a revolutionary development which raises fundamental questions about the nature of social life and the work of those who study it. (shrink)

Pattern-based reasons are reasons for action deriving not from the features of our own actions, but from the features of the larger patterns of action in which we might be participating. These reasons might relate to the patterns of action that will actually be carried out, or they might relate to merely hypothetical patterns. In past work, I have argued that accepting merely hypothetical pattern-based reasons, together with a plausible account of how to weigh these reasons, can lead to disastrous (...) consequences. However, in this article, I argue that this problem is not limited to hypothetical pattern-based reasons: it turns out that there are analogous issues for reasons deriving from actual patterns. I then suggest that we can avoid this problem by adopting a different account of the weight of pattern-based reasons. (shrink)

In this paper, we analyse how GPS-based navigation systems are transforming some of our intellectual virtues and then suggest two strategies to improve our practices regarding the use of such epistemic tools. We start by outlining the two main approaches in virtue epistemology, namely virtue reliabilism and virtue responsibilism. We then discuss how navigation systems can undermine five epistemic virtues, namely memory, perception, attention, intellectual autonomy, and intellectual carefulness. We end by considering two possible interlinked ways of trying to remedy (...) this situation: [i] redesigning the epistemic tool to improve the epistemic virtues of memory, perception, and attention; and [ii] the cultivation of cognitive diligence for wayfinding tasks scaffolding intellectual autonomy and carefulness. (shrink)

Recent discussions of emergence in physics have focussed on the use of limiting relations, and often particularly on singular or asymptotic limits. We discuss a putative example of emergence that does not fit into this narrative: the case of phonons. These quasi-particles have some claim to be emergent, not least because the way in which they relate to the underlying crystal is almost precisely analogous to the way in which quantum particles relate to the underlying quantum field theory. But there (...) is no need to take a limit when moving from a crystal lattice based description to the phonon description. Not only does this demonstrate that we can have emergence without limits, but also provides a way of understanding cases that do involve limits. (shrink)

Is life a purely physical process? What is human nature? Which of our traits is essential to us? In this volume, Daniel McShea and Alex Rosenberg – a biologist and a philosopher, respectively – join forces to create a new gateway to the philosophy of biology; making the major issues accessible and relevant to biologists and philosophers alike. Exploring concepts such as supervenience; the controversies about genocentrism and genetic determinism; and the debate about major transitions central to contemporary thinking about (...) macroevolution; the authors lay out the broad terms in which we should assess the impact of biology on human capacities, social institutions and ethical values. (shrink)

Laws of nature take center stage in philosophy of science. Laws are usually believed to stand in a tight conceptual relation to many important key concepts such as causation, explanation, confirmation, determinism, counterfactuals etc. Traditionally, philosophers of science have focused on physical laws, which were taken to be at least true, universal statements that support counterfactual claims. But, although this claim about laws might be true with respect to physics, laws in the special sciences (such as biology, psychology, economics etc.) (...) appear to have—maybe not surprisingly—different features than the laws of physics. Special science laws—for instance, the economic law “Under the condition of perfect competition, an increase of demand of a commodity leads to an increase of price, given that the quantity of the supplied commodity remains constant” and, in biology, Mendel's Laws—are usually taken to “have exceptions”, to be “non-universal” or “to be ceteris paribus laws”. How and whether the laws of physics and the laws of the special sciences differ is one of the crucial questions motivating the debate on ceteris paribus laws. Another major, controversial question concerns the determination of the precise meaning of “ceteris paribus”. Philosophers have attempted to explicate the meaning of ceteris paribus clauses in different ways. The question of meaning is connected to the problem of empirical content, i.e., the question whether ceteris paribus laws have non-trivial and empirically testable content. Since many philosophers have argued that ceteris paribus laws lack empirically testable content, this problem constitutes a major challenge to a theory of ceteris paribus laws. (shrink)

A number of companies including Google and BMW are currently working on the development of autonomous cars. But if fully autonomous cars are going to drive on our roads, it must be decided who is to be held responsible in case of accidents. This involves not only legal questions, but also moral ones. The first question discussed is whether we should try to design the tort liability for car manufacturers in a way that will help along the development and improvement (...) of autonomous vehicles. In particular, Patrick Lin’s concern that any security gain derived from the introduction of autonomous cars would constitute a trade-off in human lives will be addressed. The second question is whether it would be morally permissible to impose liability on the user based on a duty to pay attention to the road and traffic and to intervene when necessary to avoid accidents. Doubts about the moral legitimacy of such a scheme are based on the notion that it is a form of defamation if a person is held to blame for causing the death of another by his inattention if he never had a real chance to intervene. Therefore, the legitimacy of such an approach would depend on the user having an actual chance to do so. The last option discussed in this paper is a system in which a person using an autonomous vehicle has no duty of interfering, but is still held responsible for possible accidents. Two ways of doing so are discussed, but only one is judged morally feasible. (shrink)

Hans Blumenberg did not formulate a theory of reading, but in his dissertation of 1946-47 he had already established a connection between reception and theory formation. This can be traced through the history of metaphor from the "Book of Nature" to the late glosses. This study describes the importance of reading for Blumenberg's writings, developing a post-hermeneutic concept of readability.

In the Critique of Pure Reason, Kant states that ideas give us the rule for organizing experience and ideals serve as archetypes or standards against which one can measure copies. Further, he states that ideas and ideals can be practical. Understanding how precisely these concepts should function presents a challenging and understudied philosophical puzzle. I offer a reconstruction of how ideas and ideals might be practical in order to uphold, to my mind, a conceptually worthy distinction. A practical idea, I (...) argue, is best understood as a reference to the categorical imperative (and its various formulations), which guides conduct directly as a rule. A practical ideal, by contrast, I think is a substrate that serves two functions: one that (a) helps us gauge moral deficiencies and another that (b) reveals the potential for moral improvement. In response to well-grounded sceptical concerns, I argue that ideals are indirectly practical in that they ground the possibility to recognise moral states of affairs and be moral in the first place. (shrink)

In this paper, we argue that a distinction ought to be drawn between two ways in which a given world might be logically impossible. First, a world w might be impossible because the laws that hold at w are different from those that hold at some other world (say the actual world). Second, a world w might be impossible because the laws of logic that hold in some world (say the actual world) are violated at w. We develop a novel (...) way of modelling logical possibility that makes room for both kinds of logical impossibility. Doing so has interesting implications for the relationship between logical possibility and other kinds of possibility (for example, metaphysical possibility) and implications for the necessity or contingency of the laws of logic. (shrink)

The recent literature abounds with accounts of the semantics and pragmatics of so-called predicates of personal taste, i.e. predicates whose application is, in some sense or other, a subjective matter. Relativism and contextualism are the major types of theories. One crucial difference between these theories concerns how we should assess previous taste claims. Relativism predicts that we should assess them in the light of the taste standard governing the context of assessment. Contextualism predicts that we should assess them in the (...) light of the taste standard governing the context of use. We show in a range of experiments that neither prediction is correct. People have no clear preferences either way and which taste standard they choose in evaluating a previous taste claim crucially depends on whether they start out with a favorable attitude towards the object in question and then come to have an unfavorable attitude or vice versa. We suggest an account of the data in terms of what we call hybrid relativism. (shrink)

Achieving space domain awareness requires the identification, characterization, and tracking of space objects. Storing and leveraging associated space object data for purposes such as hostile threat assessment, object identification, and collision prediction and avoidance present further challenges. Space objects are characterized according to a variety of parameters including their identifiers, design specifications, components, subsystems, capabilities, vulnerabilities, origins, missions, orbital elements, patterns of life, processes, operational statuses, and associated persons, organizations, or nations. The Space Object Ontology provides a consensus-based realist framework (...) for formulating such characterizations in a computable fashion. Space object data are aligned with classes and relations in the Space Object Ontology and stored in a dynamically updated Resource Description Framework triple store, which can be queried to support space domain awareness and the needs of spacecraft operators. This paper presents the core of the Space Object Ontology, discusses its advantages over other approaches to space object classification, and demonstrates its ability to combine diverse sets of data from multiple sources within an expandable framework. Finally, we show how the ontology provides benefits for enhancing and maintaining longterm space domain awareness. (shrink)

Can philosophy be a source of hope? Today it is common to believe that the answer is no - that providing hope, if it is possible at all, belongs either to the predictive sciences or to religion. In this exciting and simulating book, however, Alexander Douglas argues that the philosophy of Spinoza can offer something akin to religious hope. Douglas shows how Spinoza is able, without appealing to belief in any traditional afterlife or supernatural grace, to develop a profound (...) and original theory of how humans can escape from the conditions of death and sin. Douglas argues that this theory of escape, which Spinoza calls beatitude, is the centrepiece of his entire philosophy, though scholars have often downplayed or ignored it. One reason for this scholarly neglect might be the difficulty of understanding Spinoza's theory, which departs from the standard doctrines and methods of Western philosophy. Douglas's interpretation therefore seeks inspiration beyond the Western tradition, drawing especially on the classical Daoist text Zhuangzi and its commentaries. Here, Douglas argues, surprising resonances with Spinoza's core ideas can be found, leading to a new way of understanding his strange yet compelling theory of beatitude. (shrink)