Long-Term Potentiation: One Kind or Many?

Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds

Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology

Associations of Starch Gel Hardness, Granule Size, Waxy Allelic Expression, Thermal Pasting, Milling Quality, and Kernel Texture of 12 Soft Wheat Cultivars

Starches were isolated from 12 soft wheat (Triticum aestivum L.) cultivars and were characterized for waxy (Wx) allelic expression, thermal pasting characteristics, and starch granule size. Gels were produced from the thermally degraded starches and were evaluated using large deformation rheological measurements. Data were compared with cultivar kernel texture, milling characteristics, starch chemical analyses, and flour pasting characteristics. Larger flour yields were produced from cultivars that had larger starch granules. Flour yield also was correlated with lower amylose content and greater starch content. Harder starch gels were correlated with higher levels of amylose content and softer kernel texture. The cultivar Fillmore, which had a partial waxy mutation at the B locus, produced the highest peak pasting viscosity and the lowest gel hardness. Softer textured wheats had greater lipid‐complexed amylose and starch phosphorus contents and had less total starch content. Among these wheats of the soft market class, softer textured wheats had larger starch granules and harder textured wheats had smaller starch granules. In part, this may explain why soft wheats vary in texture. The smaller granules have larger surface area available for noncovalent bonding with the endosperm protein matrix and they also may pack more efficiently, producing harder endosperm.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141588/1/cche0163.pd

A discrete geometric approach for simulating the dynamics of thin viscous threads

We present a numerical model for the dynamics of thin viscous threads based on a discrete, Lagrangian formulation of the smooth equations. The model makes use of a condensed set of coordinates, called the centerline/spin representation: the kinematical constraints linking the centerline's tangent to the orientation of the material frame is used to eliminate two out of three degrees of freedom associated with rotations. Based on a description of twist inspired from discrete differential geometry and from variational principles, we build a full-fledged discrete viscous thread model, which includes in particular a discrete representation of the internal viscous stress. Consistency of the discrete model with the classical, smooth equations is established formally in the limit of a vanishing discretization length. The discrete models lends itself naturally to numerical implementation. Our numerical method is validated against reference solutions for steady coiling. The method makes it possible to simulate the unsteady behavior of thin viscous jets in a robust and efficient way, including the combined effects of inertia, stretching, bending, twisting, large rotations and surface tension

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Teleology and Realism in Leibniz's Philosophy of Science

This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz