Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy

Protein folding is inherently a heterogeneous process because of the very large number of microscopic pathways that connect the myriad unfolded conformations to the unique conformation of the native structure. In a first step towards the long-range goal of describing the distribution of pathways experimentally, F?rster resonance energy transfer (FRET) has been measured on single, freely diffusing molecules. Here we use this method to determine properties of the free-energy surface for folding that have not been obtained from ensemble experiments. We show that single-molecule FRET measurements of a small cold-shock protein expose equilibrium collapse of the unfolded polypeptide and allow us to calculate limits on the polypeptide reconfiguration time. From these results, limits on the height of the free-energy barrier to folding are obtained that are consistent with a simple statistical mechanical model, but not with the barriers derived from simulations using molecular dynamics. Unlike the activation energy, the free-energy barrier includes the activation entropy and thus has been elusive to experimental determination for any kinetic process in solution.     

Notes on Viscainopelmatus davewerneri (Orthoptera: Gryllacrididae; Stenopelmatinae) from the Viscaino Desert, Baja California Sur, Mexico

A male nymph in stadium 3 of Viscainopelmatus davewerneri Tinkham is reported and illustrated. The specimen was taken near Laguna Scammon, Baja California Sur, Mexico.     

Description of a Phyllorhynchus from Cerralvo Island, Gulf of California, Mexico

Phyllorhynchus decurtatus porelli ssp. nov. is described from a single specimen from Cerralvo Island, Gulf of California, Mexico, and is regarded as different from P. d. decuratus on the basis of an increased number of dorsal blotches (41 as compared to 18 – 33) and an increased number of supralabials (7 as compared to 6), combined with geographical isolation and the high degree of endemism found in other reptiles on Cerralvo Island.       

Thomas Reid and the problem of induction: from common experience to common sense

By the middle of the eighteenth century the new science had challenged the intellectual primacy of common experience in favor of recondite, expert and even counter-intuitive knowledge increasingly mediated by specialized instruments. Meanwhile modern philosophy had also problematized the perceptions of common experience — in the case of David Hume this included our perception of causal relations in nature, a fundamental precondition of scientific endeavor.In this article I argue that, in responding to the ‘problem of induction’ as advanced by Hume, Reid reformulated Aristotelian foundationalism in distinctly modern terms. An educator and mathematician self-consciously working within the framework of the new science, Reid articulated a philosophical foundation for natural knowledge anchored in the human constitution and in processes of adjudication in an emerging modern public sphere of enlightened discourse. Reid thereby transformed one of the bases of Aristotelian science — common experience — into a philosophically and socially justified notion of ‘common sense’. Reid's intellectual concerns had as much to do with the philosophy of science as they did with moral philosophy or epistemology proper, and were bound up with wider social and scientific changes taking place in the early modern period.     

Architecture and Technology: A Discontinuous Relation

Technology has a history structured by discontinuities. The first important philosophical expression of such a conception of technology was advanced by Walter Benjamin when he defined art works in relation to specific techniques of production. At the present art and architecture occur within an age defined by the move from ’technical reproducibility’ to digital reproducibility. The move has an impact on how technology is understood and its relation to architecture conceived. Adapting Walter Benjamin’s work in this area provides the basis for a response to Soren Riis’ important treatment of the relationship between architecture and technology in his paper “Dwelling in-between walls: the architectural surround”.