Explanatory asymmetries, ground, and ontological dependence

The notions of ground and ontological dependence have made a prominent resurgence in much of contemporary metaphysics. However, objections have been raised. On the one hand, objections have been raised to the need for distinctively metaphysical notions of ground and ontological dependence. On the other, objections have been raised to the usefulness of adding ground and ontological dependence to the existing store of other metaphysical notions. Even the logical properties of ground and ontological dependence are under debate. In this article, I focus on how to account for the judgements of non-symmetry in several of the cases that motivate the introduction of notions like ground and ontological dependence. By focusing on the notion of explanation relative to a theory, I conclude that we do not need to postulate a distinctively asymmetric metaphysical notion in order to account for these judgements

Causal theories of explanation and the challenge of explanatory disagreement

When evaluating the success of causal theories of explanation the focus has typically been on the legitimacy of causal relations and on putative examples of explanations that we cannot capture in causal terms. Here I motivate the existence of a third kind of problem: the difficulty of accounting for explanatory disputes. Moreover, I argue that this problem remains even if the first two are settled and that it threatens to undercut one of the central motivations for causal accounts of explanation, namely, the causal account of the directionality of scientific explanation

Explanatory asymmetries: laws of nature rehabilitated

The problem of explanatory non-symmetries provides the strongest reason to abandon the view that laws can figure in explanations without causal underpinnings. I argue that this problem can be overcome. The solution that I propose starts from noticing the importance of conditions of application when laws do explanatory work, and I go on to develop a notion of nomological (non-causal) dependence that can tackle the non-symmetry problem. The strategy is to show how a strong notion of counterfactual dependence as guaranteed by the laws is a plausible account of what we aim towards when we give law-based explanations. The aim of this project is not to deny that causal relations can do explanatory work but to restore laws of nature as capable of being explanatory even in the absence of any knowledge of causal underpinnings

Genetic modeling of the Hippo pathway in hematopoietic stem cells

Hematopoiesis is the process of blood formation from a limited pool of hematopoietic stem cells (HSCs). These rare stem cells can both self-renew to maintain the HSC pool, and differentiate to continuously replenish lost blood cells. The mechanisms of HSC regulation are not fully known. The aim of this thesis was to study the role of the Hippo signaling pathway in HSCs. The Hippo pathway is a newly discovered signaling pathway, which regulates organ size in Drosophila. Hippo signaling has further been implicated in regulation of mammalian stem cells. In Article I we developed a new way of modeling genetic changes by combining genetic engineering of murine ES cells with blastocyst complementation. This approach avoids the cost and time constraints associated with the creation of standard transgenic mouse strains while taking advantage of the sophisticated site-directed manipulations that are possible in ES cells. In Article II we studied YAP1, the downstream effector in the Hippo pathway. We created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system using the blastocyst complementation approach developed in article I. When investigating the effect of overexpressing YAP1 in HSCs we detected no effect on HSC function during steady state or regenerative stress. This is contrast to effects seen in other tissue stem cells and suggests tissue specific functions of YAP1 in regulation of stem cells. In Article III we investigated a knockout model for the other Hippo effector Taz. Adult mice deficient in Taz display no changes in hematopoietic parameters but are born below mendelian ratios. Taz thus seems dispensable for adult hematopoiesis but may influence embryonic development. Taken together, using both novel and traditional genetic engineering approaches in mice, we have taken the first steps to understand the role of the Hippo pathway in hematopoiesis

Network explanations and explanatory directionality

Network explanations raise foundational questions about the nature of scientific explanation. The challenge discussed in this article comes from the fact that network explanations are often thought to be non-causal, i.e. they do not describe the dynamical or mechanistic interactions responsible for some behaviour, instead they appeal to topological properties of network models describing the system. These non-causal features are often thought to be valuable precisely because they do not invoke mechanistic or dynamical interactions and provide insights that are not available through causal explanations. Here, I address a central difficulty facing attempts to move away from causal models of explanation; namely, how to recover the directionality of explanation. Within causal models, the directionality of explanation is identified with the direction of causation. This solution is no longer available once we move to non-causal accounts of explanation. I will suggest a solution to this problem that emphasizes the role of conditions of application. In doing so, I will challenge the idea that sui generis mathematical dependencies are the key to understand non-causal explanations. The upshot is a conceptual account of explanation that accommodates the possibility of non-causal network explanations. It also provides guidance for how to evaluate such explanations. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'

Making sense of Wnt signaling—linking hair cell regeneration to development

Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration

A thermodynamic database for simulation of CMAS and TBC interactions

A thermodynamic database has been developed for calculating thermochemical interaction of thermal barrier coatings, namely 7YSZ (yttria partially stabilized zirconia), with CaO-MgO-Al2O3-SiO2 (CMAS) deposits. CaO-MgO-Al2O3-SiO2-Y2O3-ZrO2 is thus the core system for understanding and modeling of processes occurring between CMAS and TBC. A good thermodynamic description of all phases in the system is essential in modeling related to materials design and process optimization. An efficient technique used to obtain a self-consistent thermodynamic database is called the CALPHAD method [1], where the Gibbs energy of each phase is described with a mathematical model. The Gibbs energy of the total system is then minimized with respect to temperature and composition in order to predict the most stable phases under equilibrium conditions. In this work Y2O3-ZrO2 was incorporated into an existing description [2] of the CaO-MgO-Al2O3-SiO2 system. Many pseudo-binaries and ternaries are assessed within the CaO-MgO-Al2O3-SiO2-Y2O3-ZrO2 system. Two examples on calculated phase diagrams are shown below. The compound energy formalism [3] is used to model solid oxide solutions such as spinels, monoxide, corundum, zirconia, yttria etc. The ionic two-sublattice liquid model [4,5] is used to model molten slags

Exploring response inhibition, the behavioral inhibition system and possible sex differences in athletes and non-athletes

Background: The objective of this study was to revisit the question concerning whether athletes are better than non-athletes at fundamental cognitive abilities, such as inhibitory control, in addition to also focusing on motivational dispositions and possible sex differences. Adding the latter could be crucial since both inhibitory control and motivational dispositions, such as approach and avoidance, are central to goal-directed behavior. Methods: This study’s sample was composed of 93 participants (40 males): 29 biathletes; 30 alpine skiers; and 34 non-athletes. A non-sport-specific stop-signal task was used for the assessment of inhibitory control in terms of response inhibition, and the motivational dispositions were assessed with the BIS/BAS scales. Results: The results showed that there were no differences between the two different sports or non-athletes with regard to response inhibition. However, females showed significantly slower response inhibition than males (p = 0.018) and scored significantly higher on the trait variable BIS (p < 0.001). Conclusions: The results from this study suggest that it might be meaningful to explore the contribution of sex differences and motivational dispositions on response inhibition in conjunction with different types of sports.info:eu-repo/semantics/publishedVersio

Explanatory abstractions

A number of philosophers have recently suggested that some abstract, plausibly non-causal and/or mathematical, explanations explain in a way that is radically different from the way causal explanation explain. Namely, while causal explanations explain by providing information about causal dependence, allegedly some abstract explanations explain in a way tied to the independence of the explanandum from the microdetails, or causal laws, for example. We oppose this recent trend to regard abstractions as explanatory in some sui generis way, and argue that a prominent account of causal explanation can be naturally extended to capture explanations that radically abstract away from microphysical and causal nomogical details. To this end, we distinguish different senses in which an explanation can be more or less abstract, and analyse the connection between explanations’ abstractness and their explanatory power. According to our analysis abstract explanations have much in common with counterfactual causal explanations