Two Legacies of Goldman’s Epistemology

Goldman’s epistemology has been influential in two ways. First, it has influenced some philosophers to think that, contrary to erstwhile orthodoxy, relations of evidential support, or confirmation, are not discoverable a priori. Second, it has offered some philosophers a powerful argument in favor of methodological reliance on intuitions about thought experiments in doing philosophy. This paper argues that these two legacies of Goldman’s epistemology conflict with each other

Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis

Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment. We find that CXCL10 is upregulated in metastasis-associated astrocytes in mice and humans and is functionally important for the chemoattraction of melanoma cells. Moreover, CXCR3, the receptor for CXCL10, is upregulated in brain-tropic melanoma cells. Targeting melanoma expression of CXCR3 by nanoparticle-mediated siRNA delivery or by shRNA transduction inhibits melanoma cell migration and attenuates brain metastasis in vivo. These findings suggest that the instigation of pro-inflammatory signaling in astrocytes is hijacked by brain-metastasizing tumor cells to promote their metastatic capacity and that the CXCL10-CXCR3 axis may be a potential therapeutic target for the prevention of melanoma brain metastasis

Relativism, Coherence, and the Problems of Philosophy *

The eventual topic of this paper is the perhaps grandiose question of whether we have any reason to think that philosophical problems can be solved. Philosophy has been around for quite some time, and its record is cause for pessimism: it is not, exactly, that there are no established results, but that what results there are, are negative (such-and-such is false, or won't work), or conditional (as Ernest Nagel used to say, "If we had ham, and if we had eggs, then we'd have ham and eggs"). 1 I hope in what follows first of all to explain the record. My explanation will naturally suggest a way of turning over a new leaf, and I will wrap up the paper by laying out that proposal and critically assessing its prospects. However, the approach to my topic will have to be roundabout. Along the way, I will detour to consider how the problems of philosophy can be * I'm grateful t