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BACKGROUND High levels of antiretroviral therapy adherence are important for human immunodeficiency virus type 1 (HIV-1) suppression, yet the magnitude of adherence required to maintain it is less well characterized. Furthermore, methods to accommodate changes in adherence over time are lacking. In the present study, our objective was to determine the(More)
The sixth transmembrane segment (TM6) of the CFTR chloride channel has been intensively investigated. The effects of amino acid substitutions and chemical modification of engineered cysteines (cysteine scanning) on channel properties strongly suggest that TM6 is a key component of the anion-conducting pore, but previous cysteine-scanning studies of TM6 have(More)
The tree of my title is not a green tree with leaves. It is the name of an abstract structure. I shall contrast it with another, more complex abstract structure called a semilattice. In order to relate these abstract structures to the nature of the city, I must first make a simple distinction. I want to call those cities which have arisen more or less(More)
High-throughput screening has led to the identification of small-molecule blockers of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, but the structural basis of blocker binding remains to be defined. We developed molecular models of the CFTR channel on the basis of homology to the bacterial transporter Sav1866, which could(More)
In this paper, I am trying to lay out a new form of computation, which focuses on the harmony reached in a system. This type of computation in some way resembles certain recent results in chaos theory and complexity theory. However, the orientation of harmony-seeking computation is toward a kind of computation which finds harmonious configurations, and so(More)
This study was designed to examine the relationship between untimed antiretroviral concentrations measured in plasma samples collected for virus-load testing and response to highly active antiretroviral therapy. Plasma nonnucleoside reverse-transcriptase-inhibitor and protease-inhibitor concentrations were retrospectively measured in all virus-load plasma(More)
We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the prokaryotic ABC transporter, Sav1866. Here we analyze predicted pore geometry and side-chain orientations for TM3, TM6, TM9, and TM12, with particular attention being paid to the location of the rate-limiting barrier for anion conduction.(More)