Modeling Ensembles of Enzyme Reaction Pathways with Hi-MSM Reveals the Importance of Accounting for Pathway Diversity.

Conventional quantum mechanical-molecular mechanics (QM/MM) simulation approaches for modeling enzyme reactions often assume that there is one dominant reaction pathway and that this pathway can be sampled starting from an X-ray structure of the enzyme. These assumptions reduce computational cost; however, their validity has not been extensively tested. This is due in part to the lack of a rigorous formalism for integrating disparate pathway information from dynamical QM/MM calculations.

Hierarchical Markov State Model Building to Describe Molecular Processes.

Markov state models can describe ensembles of pathways via kinetic networks but are difficult to create when large free-energy barriers limit unbiased sampling. Chain-of-states simulations allow sampling over large free-energy barriers but are often constructed using a single pathway that is unlikely to thermodynamically average over orthogonal degrees of freedom in complex systems. Here, we combine the advantages of these two approaches in the form of a Markov state model of Markov state models, which we call a Hierarchical Markov state model.

Erythrocyte lysis and Xenopus laevis oocyte rupture by recombinant Plasmodium falciparum hemolysin III.

Malaria kills more than 1 million people per year worldwide, with severe malaria anemia accounting for the majority of the deaths. Malaria anemia is multifactorial in etiology, including infected erythrocyte destruction and decrease in erythrocyte production, as well as destruction or clearance of noninfected erythrocytes. We identified a panspecies Plasmodium hemolysin type III related to bacterial hemolysins.

Explaining skin permeation of 2-butoxyethanol from neat and aqueous solutions.

Absorption of 2-butoxyethanol (BE) from neat and aqueous solutions of BE was measured through rat skin in vitro and in vivo and through silicone membranes. Like previous studies in human and guinea pig skin, BE flux increased proportional to BE concentration only when the weight fraction of BE (w(BE)) View Article and Find Full Text PDF

Thy-1 expression on blast cells from adult patients with acute myeloid leukemia.

Bone marrow and peripheral blood from 28 adult patients with acute myeloid leukemia (AML) were analyzed for the surface expression of the Thy-1 antigen by dual-colour flow cytometry. The Thy-1 antigen was expressed on greater than 5% of cells from seven patients with the proportions of Thy-1 positive cells ranging from 8.1% to 85.

Phase I clinical trial of serotherapy in patients with acute myeloid leukemia with an immunoglobulin M monoclonal antibody to CD15.

Sixteen patients with acute myeloid leukemia (AML) were treated with a continuous i.v. infusion of mAb PM-81, an IgM mAb directed against the cellular differentiation antigen CD15, which is expressed on leukemia cells of >95% of patients with AML.

A unique population of CD34+ cells in cord blood.

Human umbilical cord blood (CB) is a rich source of hematopoietic stem cells for both research and stem cell transplantation. In clinical studies, it appears that recovery from myeloablative therapy using CB requires significantly fewer cells than a typical allogeneic marrow transplant. This suggests that CB may be enriched for early hematopoietic progenitors.