Aristotle on Mind and the Science of Nature

On the basis of two premises to which he is committed, it would seem that Aristotle must be a “naturalist” about the investigation of the soul: 1. Natural things have both a material and a formal nature. 2. In the case of living things, their formal nature is their soul. This paper deals with a complication in the above inference. In De partibus animalium I 1, Aristotle insists that the natural scientist should not speak of all soul, since not all of the soul is a nature, though one or more parts of it is (641b8–9). In this paper I argue that this claim is consistent with everything he says in the De anima about the investigation of reason, and is a consequence of his views about the methodological norms of natural science. Aristotle is a naturalist when it comes to those parts of the soul human beings share with other animals, but his views about the mind are much more complicated

Aristotle and the Functions of Reproduction

I shall argue that the function of the reproductive capacity is not to perpetuate the kind (or species), but to allow the individual reproducer to be eternal: not eternal without qualifications, but in a way. The basic premise in the arguments which establish this conclusion distinguishes between things which are numerically eternal and those which are formally eternal. This of this latter sort must be members of an everlasting series of individuals which are one-in-form (ἕν εἴδει, in Aristotle\u27s usage). The full understanding of these passages, therefore, requires a proper interpretation of the distinction between numerical and formal unity. with this distinction clarified, and with a better understanding of Aristotle\u27s teleological explanations of reproduction and sex, i close by suggesting another \u27function\u27 of reproduction - eliminating forms as independent paradigms for natural substances

Aristotle and Darwin: Antagonists or Kindred Spirits?

In the decades following the forging of the so-called Neo-Darwinian Synthesis in the 1940s, a number of its philosophical defenders created a myth about what Charles Darwin was up against, a viewpoint called “typological essentialism” often attributed to Aristotle. In this paper I first sketch the history of how this myth was created. I then establish that it is a myth by providing an account of Aristotle’s essentialism as it is actually displayed in his philosophy of biology and in his biological practice. It has nothing to do with the ‘mythic’ version. We then turn to what Darwin was really up against—a common, anti-evolutionary way of defining the species concept in Darwin’s time (that owes nothing to Aristotle), and to his attempts to re-orient thinking about it. I will close by reconsidering Aristotle and Charles Darwin: Does it make any sense to think about the relationship between two thinkers separated by more than two millennia living in such vastly different cultures? What did Charles Darwin himself think about Aristotle

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2\u27-O-Methyl (2\u27OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2\u27OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages. Interspecies conservation of this inhibitory activity was confirmed on TLR7/8 activity in human peripheral blood mononuclear cells. Significantly, we identified a core motif governing the inhibitory activity of these AMOs, which is present in more than 50 AMOs targeted to human miRNAs in miRBaseV20. DNA/locked nucleic acids (LNA) AMOs synthesized with a phosphorothioate backbone also inhibited TLR7 sensing in a sequence-dependent manner, demonstrating that the off-target effects of AMOs are not restricted to 2\u27OMe modification. Taken together, our work establishes the potential for off-target effects of AMOs on TLR7/8 function, which should be taken into account in their therapeutic development and in vivo application

The Role of Industry, Geography and Firm Heterogeneity in Credit Risk Diversification

In theory the potential for credit risk diversification for banks could be substantial. Portfolio diversification is driven broadly by two characteristics: the degree to which systematic risk factors are correlated with each other and the degree of dependence individual firms have to the different types of risk factors. We propose a model for exploring these dimensions of credit risk diversification: across industry sectors and across different countries or regions. We find that full firm-level parameter heterogeneity matters a great deal for capturing differences in simulated credit loss distributions. Imposing homogeneity results in overly skewed and fat-tailed loss distributions. These differences become more pronounced in the presence of systematic risk factor shocks: increased parameter heterogeneity greatly reduces shock sensitivity. Allowing for regional parameter heterogeneity seems to better approximate the loss distributions generated by the fully heterogeneous model than allowing just for industry heterogeneity. The regional model also exhibits less shock sensitivity

Potentiality in Aristotle's psychology and ethics

The distinction between potentiality and actuality in Aristotle has its origin in Platonic ethics. In his psychological and ethical works Aristotle’s notion of potentiality is embedded in a causal framework that is characteristic of life in general. A key theme is the distinction of various meanings of ‘to know’. In his early work the possession of knowledge is distinguished from its use. In De anima Aristotle adds the potentiality for acquiring knowledge as characteristic of the genus human being. He argues that the stages of actualization of knowledge are instances of a more comprehensive biological and ethical development. Life is the fulfillment of soul as formal, efficient and final cause, with the potentiality of body as material cause. The unity of body and soul is derived from the causal nexus of potentiality and actuality, like a power and the instrument in which it resides. In such cases potentiality is complex and depends on numerous conditions. Failure of full realization may occur when any of the necessary conditions of the development and realization of the fulfillment of human life are lacking, whether in the environment (e.g. climate), the body (illness, drunkenness), or the soul (natural virtue, firm character, attention).Political Philosophy and Ethic

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms