157 research outputs found
Evaluating the transferability of coarse-grained, density-dependent implicit solvent models to mixtures and chains
Previously, we described a coarse-graining method for creating local density-dependent implicit solvent (DDIS) potentials that reproduce the radial distribution function (RDF) and solute excess chemical potential across a range of particle concentrations [ E. C. Allen and G. C. Rutledge, J. Chem. Phys. 128, 154115 (2008) ]. In this work, we test the transferability of these potentials, derived from simulations of monomeric solute in monomeric solvent, to mixtures of solutes and to solute chains in the same monomeric solvent. For this purpose, “transferability” refers to the predictive capability of the potentials without additional optimization. We find that RDF transferability to mixtures is very good, while RDF errors in systems of chains increase linearly with chain length. Excess chemical potential transferability is good for mixtures at low solute concentration, chains, and chains of mixed composition; at higher solute concentrations in mixtures, chemical potential transferability fails due to the nature of the DDIS potentials, in which particle insertion directly affects the interaction potential. With these results, we demonstrate that DDIS potentials derived for pure solutes can be used effectively in the study of many important systems including those involving mixtures, chains, and chains of mixed composition in monomeric solvent.United States. Dept. of Energy (Computational Sciences Graduate Fellowship
What information theory can tell us about quantum reality
An investigation of Einstein's ``physical'' reality and the concept of
quantum reality in terms of information theory suggests a solution to quantum
paradoxes such as the Einstein-Podolsky-Rosen (EPR) and the Schroedinger-cat
paradoxes. Quantum reality, the picture based on unitarily evolving
wavefunctions, is complete, but appears incomplete from the observer's point of
view for fundamental reasons arising from the quantum information theory of
measurement. Physical reality, the picture based on classically accessible
observables is, in the worst case of EPR experiments, unrelated to the quantum
reality it purports to reflect. Thus, quantum information theory implies that
only correlations, not the correlata, are physically accessible: the mantra of
the Ithaca interpretation of quantum mechanics.Comment: LaTeX with llncs.cls, 11 pages, 6 postscript figures, Proc. of 1st
NASA Workshop on Quantum Computation and Quantum Communication (QCQC 98
Coarse-graining strategies in polymer solutions
We review a coarse-graining strategy (multiblob approach) for polymer
solutions in which groups of monomers are mapped onto a single atom (a blob)
and effective blob-blob interactions are obtained by requiring the
coarse-grained model to reproduce some coarse-grained features of the
zero-density isolated-chain structure. By tuning the level of coarse graining,
i.e. the number of monomers to be mapped onto a single blob, the model should
be adequate to explore the semidilute regime above the collapse transition,
since in this case the monomer density is very small if chains are long enough.
The implementation of these ideas has been previously based on a
transferability hypothesis, which was not completely tested against
full-monomer results (Pierleoni et al., J. Chem. Phys, 127, 171102 (2007)). We
study different models proposed in the past and we compare their predictions to
full-monomer results for the chain structure and the thermodynamics in the
range of polymer volume fractions \Phi between 0 and 8. We find that the
transferability assumption has a limited predictive power if a
thermodynamically consistent model is required. We introduce a new tetramer
model parametrized in such a way to reproduce not only zero-density
intramolecular and intermolecular two-body probabilities, but also some
intramolecular three-body and four-body distributions. We find that such a
model correctly predicts three-chain effects, the structure and the
thermodynamics up to \Phi ~ 2, a range considerably larger than that obtained
with previous simpler models using zero-density potentials. Our results show
the correctness of the ideas behind the multiblob approach but also that more
work is needed to understand how to develop models with more effective monomers
which would allow us to explore the semidilute regime at larger chain volume
fractions.Comment: 33 pages, 19 figures, submitted to Soft Matte
Novel highly potent CD4bs bNAb with restricted pathway to HIV-1 escape
Purpose: Broadly HIV-1 neutralizing antibodies (bNAbs) can suppress viremia
in humans and represent a novel approach for effective immunotherapy.
However, bNAb monotherapy selects for antibody-resistant viral variants.
Thus, we focused on the identification of new antibody combinations and/or
novel bNAbs that restrict pathways of HIV-1 escape.
Methods: We screened HIV-1 positive patients for their neutralizing
capacities. Following, we performed single cell sorting and PCR of HIV-1
Env-reactive mature B cells of identified elite neutralizers. Found antibodies
were tested for neutralization and binding capacities in vitro. Further, their
antiviral activity was tested in an HIV-1 infected humanized mouse model.
Results: Here we report the isolation of antibody 1–18, a VH1–46-encoded
CD4 binding site (CD4bs) bNAb identified in an individual ranking among the
top 1% neutralizers of 2,274 HIV-1-infected subjects. Tested on a 119-virus
panel, 1–18 showed to be exceptionally broad and potent with a coverage of
97% and a mean IC50 of 0.048 lg/mL, exceeding the activity of most potent
CD4bs bNAbs described to-date. A 2.4 Å cryo-EM structure of 1–18 bound to a
native-like Env trimer revealed that it interacts with HIV-1 env similar to other
CD4bs bNAbs, but includes additional contacts to the V3 loop of the adjacent
protomer. Notably, in vitro, 1–18 maintained activity against viruses carrying
mutations associated with escape from VRC01-class bNAbs. Further, its HIV-1
env wide escape profile differed critically from other CD4bs bNAbs. In
humanized mice, monotherapy with 1–18 was sufficient to prevent the
development of viral escape variants that rapidly emerged during treatment
with other CD4bs bNAbs. Finally, 1–18 overcame classical HIV-1 mutations
that are driven by VRC01-like bNAbs in vivo.
Conclusion: 1–18 is a highly potent and broad bNAb that restricts escape and
overcomes frequent CD4bs escape pathways, providing new options for bNAb
combinations to prevent and treat HIV-1 infection
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