Toward a Lockean Unification of Formal and Traditional Epistemology

Can there be knowledge and rational belief in the absence of a rational degree of confidence? Yes, and cases of "mistuned knowledge" demonstrate this. In this paper we leverage this normative possibility in support of advancing our understanding of the metaphysical relation between belief and credence. It is generally assumed that a Lockean metaphysics of belief that reduces outright belief to degrees of confidence would immediately effect a unification of coarse-grained epistemology of belief with fine-grained epistemology of confidence. Scott Sturgeon has suggested that the unification is effected by understanding the relation between outright belief and confidence as an instance of the determinable-determinate relation. But determination of belief by confidence would not by itself yield the result that norms for confidence carry over to norms for outright belief unless belief and high confidence are token identical. We argue that this token-identity thesis is incompatible with the neglected phenomenon of “mistuned knowledge”—knowledge and rational belief in the absence of rational confidence. We contend that there are genuine cases of mistuned knowledge and that, therefore, epistemological unification must forego token identity of belief and high confidence. We show how partial epistemological unification can be secured given determination of outright belief by degrees of confidence even without token-identity. Finally, we suggest a direction for the pursuit of thoroughgoing epistemological unification

Stimulation of Piezo1 by mechanical signals promotes bone anabolism

Mechanical loading, such as caused by exercise, stimulates bone formation by osteoblasts and increases bone strength, but the mechanisms are poorly understood. Osteocytes reside in bone matrix, sense changes in mechanical load, and produce signals that alter bone formation by osteoblasts. We report that the ion channel Piezo1 is required for changes in gene expression induced by fluid shear stress in cultured osteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient to replicate the effects of fluid flow on osteocytes. Conditional deletion o

Formation of Dark Matter Haloes in a Homogeneous Dark Energy Universe

Several independent cosmological tests have shown evidences that the energy density of the Universe is dominated by a dark energy component, which cause the present accelerated expansion. The large scale structure formation can be used to probe dark energy models, and the mass function of dark matter haloes is one of the best statistical tools to perform this study. We present here a statistical analysis of mass functions of galaxies under a homogeneous dark energy model, proposed in the work of Percival (2005), using an observational flux-limited X-ray cluster survey, and CMB data from WMAP. We compare, in our analysis, the standard Press-Schechter (PS) approach (where a Gaussian distribution is used to describe the primordial density fluctuation field of the mass function), and the PL (Power Law) mass function (where we apply a nonextensive q-statistical distribution to the primordial density field). We conclude that the PS mass function cannot explain at the same time the X-ray and the CMB data (even at 99% confidence level), and the PS best fit dark energy equation of state parameter is $\omega=-0.58$, which is distant from the cosmological constant case. The PL mass function provides better fits to the HIFLUGCS X-ray galaxy data and the CMB data; we also note that the $\omega$ parameter is very sensible to modifications in the PL free parameter, $q$, suggesting that the PL mass function could be a powerful tool to constrain dark energy models.Comment: 4 pages, 2 figures, Latex. Accepted for publication in the International Journal of Modern Physics D (IJMPD)

In-Vivo Nucleus Pulposus-Specific Regulation of Adult Murine Intervertebral Disc Degeneration via Wnt/Beta-Catenin Signaling

B-Catenin, transcription factor of Wnt signaling, is promoted in patients with intervertebral disc (IVD) degeneration, but Wnt signaling decreases with aging. We hypothesize that IVD degeneration is associated with decreased Wnt signaling despite more b-Catenin. Chronic compression of tail IVDs of young-adult and aged Wnt-reporter (TOPGAL) animals initiated an age-related cascade of degenerative-like changes, which included reduced Wnt ligand expression and Wnt signaling in nucleus pulposus cells, despite elevation of b-Catenin protein and gene expression. To determine the effect of upregulated and downregulated Wnt signaling in adult discs, b-Catenin in the nucleus pulposus was stabilized (Shh-CreErT2/b-Cateninfl(Ex3)/fl(Ex3), cACT) or knocked out (Shh-CreErT2/b-Cateninfl/fl, cKO). cACT discs had promoted expression of Wnt-targets and -ligands, brachyury, extracellular matrix production and 34% greater compressive stiffness than WT (b-Cateninfl(Ex3)/fl(Ex3)) discs, but 50% less tensile stiffness. By contrast, knockout reversed the cACT phenotype: less protein expression of b-catenin in the nucleus pulposus, less expression of brachyury, heightened expression of extracellular matrix breakdown and 46% less compressive stiffness than wild-type (b-Cateninfl/fl,WT) discs. These data suggest that intervertebral disc degeneration is associated with loss of Wnt signaling and that the concomitant increase in b-catenin is a regenerative response, potentially offering a therapeutic approach to degeneration