MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub (...) that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. (shrink)

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under‐investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immune‐modulatory properties, including the creation of an immunoinhibitory, immune‐privileged milieu, we propose a novel hypothesis taking into account the role of the hair follicle. We hypothesize that the changes and imbalance of (...) yeast and bacterial species, along with increasing proinflammatory sebum by‐products, leads to the activation of immune response and inflammation. Hair follicle keratinocytes may then detect these changes in scalp microbiota resulting in the recruitment of leukocytes to the inflammation site. These changes in the scalp skin immune‐microenvironment may impact hair follicle immune privilege status, which opens new avenues into exploring the role of the hair follicle in dandruff pathogenesis. Also see the video abstract here: https://youtu.be/mEZEznCYtNs. (shrink)

This article explores impact investing within the renewable energy sector. Drawing on ethical decision making and sensemaking, this article contributes to an enhanced understanding of the complex ethical sensemaking process of impact investors when facing plausible situations in a world of contested truths. Addressing the ethical tensions faced by impact investors with mixed motives, this study investigates the way decision makers use context-specific reasons to make sense of and shape the renewable energy investment process. This represents an initial attempt to (...) understand ethical sensemaking in impact investing made within the renewable energy sector using a multi-stakeholder approach. Our findings show that prosocial, personal, reputational, and economic motives are the main drivers of REI, with prosocial and personal motives being value-based, and reputational and economic motives being evidence-based. We find three different modes of ethical sensemaking, allowing for the construction of the four motives noted above. These motives are based on the context-specific reasons of impact investing decision makers in the RE sector. This article contributes to the academic discourse on ethical sensemaking with some key processes involved in ethical decision making, and a better understanding of the underlying motivations of impact investing in the RE sector. (shrink)

Gastrulation is the process of early development that reorganizes cells into the three fundamental tissue types of ectoderm, mesoderm, and endoderm. It is a coordinated series of morphogenetic and molecular changes that exemplify many developmental phenomena. In this review, we explore one of the classic developmental systems, the sea urchin embryo, where investigators from different backgrounds have converged on a common interest to study the origin, morphogenesis, and developmental regulation of the endoderm. The sea urchin embryo is remarkably plastic in (...) its developmental potential, and the endoderm is especially instructive for its morphological and molecular responsiveness to inductive cell interactions. We start by examining and integrating the several models for the morphogenetic mechanisms of invagination and tissue elongation, the basic processes of endoderm morphogenesis in this embryo. We next critique the proposed mechanisms of inductive gene regulation in the endoderm that exemplifies a concept of modular transcriptional regulation. Finally, we end with an examination of the current molecular models to explain cell fate determination of the endoderm. Recent progress at the molecular level should soon allow us to explain the seminal experimental observations made in this embryo over a hundred years ago. BioEssays 21:459–471, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The problem of adaptive finite-time fault-tolerant control and output constraints for a class of uncertain nonlinear half-vehicle active suspension systems are investigated in this work. Markovian variables are used to denote in terms of different random actuators failures. In adaptive backstepping design procedure, barrier Lyapunov functions are adopted to constrain vertical motion and pitch motion to suppress the vibrations. Unknown functions and coefficients are approximated by the neural network. Assisted by the stochastic practical finite-time theory and FTC theory, the proposed (...) controller can ensure systems achieve stability in a finite time. Meanwhile, displacement and pitch angle in systems would not violate their maximum values, which imply both ride comfort and safety have been enhanced. In addition, all the signals in the closed-loop systems can be guaranteed to be semiglobal finite-time stable in probability. The simulation results illustrate the validity of the established scheme. (shrink)

Bank competition promotes enterprises to obtain credit funds through market mechanisms, and a combination of industry and finance has an important influence on establishing bank-enterprise relationship. Based on data of 2,245 manufacturing enterprises and branches of commercial banks in China from 2007 to 2019, this research establishes a moderated mediation model to verify whether CIF has a moderating effect on bank competition on enterprise innovation. The results are as follows. First, bank competition can both directly and indirectly promote enterprise innovation (...) by alleviating financing constraints. Second, CIF has no moderating effect on the direct effect of bank competition on enterprise innovation but has a negative moderating effect on the first half of mediating effect. (shrink)

Biologists studying complex causal systems typically identify some factors as causes and treat other factors as background conditions. For example, when geneticists explain biological phenomena, they often foreground genes and relegate the cellular milieu to the background. But factors in the milieu are as causally necessary as genes for the production of phenotypic traits, even traits at the molecular level such as amino acid sequences. Gene-centered biology has been criticized on the grounds that because there is parity among causes, the (...) “privileging” of genes reflects a reductionist bias, not an ontological difference. The idea that there is an ontological parity among causes is related to a philosophical puzzle identified by John Stuart Mill: what, other than our interests or biases, could possibly justify identifying some causes as the actual or operative ones, and other causes as mere background? The aim of this paper is to solve this conceptual puzzle and to explain why there is not an ontological parity among genes and the other factors. It turns out that solving this puzzle helps answer a seemingly unrelated philosophical question: what kind of causal generality matters in biology? (shrink)

This paper takes the form of a critical discussion of Crispin Wright’s notion of entitlement of cognitive project. I examine various strategies for defending the claim that entitlement can make acceptance of a proposition epistemically rational, including one which appeals to epistemic consequentialism. Ultimately, I argue, none of these strategies is successful, but the attempt to isolate points of disagreement with Wright issues in some positive proposals as to how an epistemic consequentialist should characterize epistemic rationality.

This volume contains C. D. Broad's Cambridge lectures on Ethics. Broad gave a course of lectures on the subject, intended primarily for Part I of the Moral Sciences Tripos, every academic year from 1933 - 34 up to and in cluding 1952 - 53 (except that he did not lecture on Ethics in 1935 - 36). The course however was frequently revised, and the present version is es sentially that which he gave in 1952 - 53. Broad always wrote out (...) his lectures fully beforehand, and the manuscript on Ethics, although full of revisions, is in a reasonably good state. But his handwriting is small and close and in places difficult to decipher. I therefore fear that some words may have been misread. There was an additional complication. In the summer of 1953 Broad revised and enlarged two sections of the course, namely the section on "Moore's theory" and that on "Naturalistic theories" (both sections occur in Chapter 4). The revised version of the section on Moore is undoubtedly superior to the earlier version, and I have therefore included it. But in my opinion this is not true of the new version of the section on naturalistic theories: although more comprehensive than the earlier version, it is not only repetitive in itself, but also repeats, sometimes almost verbatim, passages which occur elsewhere in the lectures. In brief, the new version is not fully integrated with the rest of the course. (shrink)

We introduce a novel point of view on the “models as mediators” framework in order to emphasize certain important epistemological questions about models in science which have so far been little investigated. To illustrate how this perspective can help answer these kinds of questions, we explore the use of simplified models in high energy physics research beyond the Standard Model. We show in detail how the construction of simplified models is grounded in the need to mitigate pressing epistemic problems concerning (...) the uncertainty inherent in the present theoretical and experimental contexts. (shrink)

C. S. Lewis takes us on a profound journey through both heaven and hell in this engaging allegorical tale. Using his extraordinary descriptive powers, Lewis introduces us to supernatural beings who will change the way we think about good and evil.

Argues (1) that the debate between actualists and possibilists in deontic logic distorts what is really at issue, and (2) that reframing the debate as being about reasons strongly suggests that those with possibilist sympathies should adopt more moderate claims (which may nevertheless be distinct from actualism).

Okasha claims at the outset of his book "Evolution and the Levels of Selection" that the Price equation lays bare the fundamentals underlying all selection phenomena. However, the thoroughness of his subsequent analysis of multi-level selection theories leads him to abandon his fundamentalist commitments. At critical points he invokes cost benefit analyses that sometimes favors the Price approach and sometimes the contextual approach, sometimes favors MLS1 and sometimes MLS2. And although he doesn’t acknowledge it, even the Price approach breaks down (...) into a family of alternative equations that parse the causes in different ways, none of which is uniquely correct and none of which achieves the ultimate isolation of effects due to what Okasha believes are the fundamental causes. I argue that his book provides good reason to re-conceive our understanding of evolutionary theorizing in terms of a toolbox view and to stop subjecting the analyses of evolutionary concepts to a universalist standard. (shrink)

A philosophical theory of explanation should provide solutions to a series of problems, both descriptive and normative. The aim of this essay is to establish the claim that this can be best done if one theorizes in terms of explanatory games rather than focusing on the explication of the concept of explanation. The position that is adopted is that of an explanatory pluralism and it is elaborated in terms of the rules that incorporate the normative standards that guide the processes (...) of discovery and justification of explanations as well as the modes of their communication, dissemination, and adoption. They constitute the rules of the explanatory game that the participants are playing. The philosophical project consists in describing and normatively appraising the rules that constitute these games. (shrink)

Judgement, perception, and other mental states and events have a minimal objectivity in this sense: making the judgement or being in the mental state does not in general thereby make the judgement correct or make the perception veridical. I offer an explanation of this minimal objectivity by developing a form of constitutive transcendental argument. The argument appeals to the proper individuation of the content of judgements and perceptions. In the case of the conceptual content of judgements, concepts are individuated by (...) their fundamental reference rules. Properly developed, this resource can be used against various forms of idealism, and to defend a conception of transcendental arguments that presupposes neither verificationism nor transcendental idealism. The article contrasts its approach with other recent transcendental treatments. It also addresses the relation between its argument and Principles of Significance. I close with a discussion of the right way of handling the extreme generality necessarily involved in transcendental reasoning. (shrink)

Peter C. Hodgson engages the speculative reconstruction of Christian theology that is accomplished by Hegel's Lectures on the Philosophy of Religion, and provides a close reading of the critical edition of the lectures. He analyses Hegel's concept of the object and purpose of the philosophy of religion, his critique of the theology of his time, his approach to Christianity within the framework of the concept of religion, his concept of God, his reconstruction of central Christian themes, and his placing of (...) Christianity among the religions of the world. Hodgson makes a case for the contemporary theological significance of Hegel by identifying currently contested sites of interpretation and their Hegelian resolution. (shrink)

I do not think that the existence of God can be proved or even that the main justification for the belief can be found in argument in the ordinary sense of that term, but I think two of the three which have, since Kant at least, been classified as the traditional arguments of natural theology have some force and are worthy of serious consideration. This consideration I shall now proceed to give. I cannot say this of the remaining one of (...) the arguments, the ‘ontological proof’, which I shall therefore not discuss here. (shrink)

ABSTRACT:The paper begins by surveying a range of possible views on the metaphysics of romantic love, organizing them as responses to a single question. It then outlines a position, constructionist functionalism, according to which romantic love is characterized by a functional role that is at least partly constituted by social matters, although this role may be realized by states that are not socially constructed.

Susan Mills and John Beatty proposed a propensity interpretation of fitness (1979) to show that Darwinian explanations are not circular, but they did not address the critics' chief complaint that the principle of the survival of the fittest is either tautological or untestable. I show that the propensity interpretation cannot rescue the principle from the critics' charges. The critics, however, incorrectly assume that there is nothing more to Darwin's theory than the survival of the fittest. While Darwinians all scoff at (...) this assumption, they do not agree about what role, if any, this principle plays in Darwin's theory of natural selection. I argue that the principle has no place in Darwin's theory. His theory does include the idea that some organisms are fitter than others. But greater reproductive success is simply inferred from higher fitness. There is no reason to embody this inference in the form of a special principle of the survival of the fittest. (shrink)

"C.E. Emmer’s article addresses the ongoing debates over how to classify and understand kitsch, from the inception of postmodern culture onwards. It is suggested that the lack of clear distinction between fine art and popular culture generates 'approaches to kitsch – what we might call 'deflationary' approaches – that conspire to create the impression that, ultimately, either 'kitsch' should be abandoned as a concept altogether, or we should simply abandon ourselves to enjoying kitschy objects as kitsch.' The author offers critical (...) insight into 'kitschy' items made in response to 9/11 and tries to examine the reception of these products through scrutinizing a selection of remarks posted by the Internet commentators." Editor Justyna Stępień's summary from her introduction to Redefining Kitsch and Camp in Literature and Culture (Newcastle upon Tyne: Cambridge Scholars Publishing, 2014), p. 2. The final pages of the chapter analyze the seemingly sweet landscape paintings of Thomas Kinkade to show the spirit of revenge their Christian coding can conceal. (shrink)

Clark Glymour has argued that hypothetico-deductivism, which many take to be an important method of scientific confirmation, is hopeless because it cannot be reconstructed in classical logic. Such reconstructions, as Glymour points out, fail to uphold the condition of relevance between theory and evidence. I argue that the source of the irrelevant confirmations licensed by these reconstructions lies not with hypothetico-deductivism itself, but with the classical logic in which it is typically reconstructed. I present a new reconstruction of hypothetico-deductivism in (...) relevance logic that does maintain the condition of relevance between theory and evidence. Hence, if hypothetico-deductivism is an important rationale in science, we have good reason to believe that the logic underlying scientific discourse is captured better by relevance logic than by its classical counterpart. (shrink)