The Correlation between Peripheral Blood Index and Immune Cell Expansion in Vietnamese Elderly Lung Cancer Patients.

(1) Background: The dysfunction and reduced proliferation of peripheral CD8+ T cells and natural killer (NK) cells have been observed in both aging and cancer patients, thereby challenging the adoption of immune cell therapy in these subjects. In this study, we evaluated the growth of these lymphocytes in elderly cancer patients and the correlation of peripheral blood (PB) indices to their expansion. (2) Method: This retrospective study included 15 lung cancer patients who underwent autologous NK cell and CD8+ T cell therapy between January 2016 and December 2019 and 10 healthy individuals. (3) Results: On average, CD8+ T lymphocytes and NK cells were able to be expanded about 500 times from the PB of elderly lung cancer subjects. Particularly, 95% of the expanded NK cells highly expressed the CD56 marker. The expansion of CD8+ T cells was inversely associated with the CD4+:CD8+ ratio and the frequency of PB-CD4+ T cells in PB. Likewise, the expansion of NK cells was inversely correlated with the frequency of PB-lymphocytes and the number of PB-CD8+ T cells. The growth of CD8+ T cells and NK cells was also inversely correlated with the percentage and number of PB-NK cells. (4) Conclusion: PB indices are intrinsically tied to immune cell health and could be leveraged to determine CD8 T and NK cell proliferation capacity for immune therapies in lung cancer patients.

Occupied-Orbital Fast Multipole Method for Efficient Exact Exchange Evaluation.

We present an efficient algorithm for computing the exact exchange contributions in the Hartree-Fock and hybrid density functional theory models on the basis of the fast multipole method (FMM). Our algorithm is based on the observation that FMM with hierarchical boxes can be efficiently used in the exchange matrix construction, when at least one of the indices of the exchange matrix is constrained to be an occupied orbital. Timing benchmarks are presented for alkane chains (C400H802 and C150H302), a graphene sheet (C150H30), a water cluster [(H2O)100], and a protein Crambin (C202H317O64N55S6). The computational cost of the far-field exchange evaluation for Crambin is roughly 3% that of a self-consistent field iteration when the multipoles up to rank 2 are used.

Combined Fragmentation Method: A Simple Method for Fragmentation of Large Molecules.

Here we present a new energy-based fragmentation method that is based on our previous work and combines the best elements of other energy-based fragmentation methods. Our new approach, termed "combined fragmentation method", is foremost simple to implement, robust, accurate, and produces small fragments, which are independent of conformation and size of the target molecule. Essentially small collections of bonded atoms in the target molecule are assigned to groups. Fragment molecules are formed by taking all bonded pairs of these groups. These fragments are then interacted with one another, and the interaction energy is simply added to the initial fragmentation energy. The method has been tested on numerous molecules of biological interest both in vacuum and in a continuum solvent.

Distributed Multipoles and Energies of Flexible Molecules.

In this work we show that energies and distributed multipoles, up to and including rank two, can be accurately determined via a modified Shepard interpolation of ab initio data for small molecules. The molecules considered here are the amino aldehydes, Gly and Ala, which may be typical smaller fragment molecules in certain molecular energy-based fragmentation schemes. The method is general and should be suitable for applications also involving crystal structure prediction, modeling molecular clusters, and Monte Carlo or molecular/reaction dynamics simulations. The configuration space covered by the interpolation includes that sampled by the Gly and Ala peptides in protein crystal structures, i.e., 12 dimensions for Gly: 3 torsion angles (φ, ψ, ω), 5 bond lengths, and 4 bond angles and 15 dimensions for Ala: 4 torsion angles, 6 bond lengths, and 5 bond angles. In this work we also describe a new method of importance, sampling the relevant configuration spaces, and show that it is possible to interpolate "axis free" multipoles.

Reaction dynamics of H(3)(+) + CO on an interpolated potential energy surface.

An accurate potential energy surface for H(3)(+) + CO has been constructed by interpolation of ab initio data. The reaction cross sections and thermal rate coefficients for the production of HCO(+) and HOC(+) have been evaluated using quasiclassical trajectory simulations.

Accurately reproducing ab initio electrostatic potentials with multipoles and fragmentation.

In this work, we show that our energy based fragmentation method (Bettens, R. P. A.; Lee, A. M. J. Phys. Chem. A 2006, 110, 8777) accurately reproduces the electrostatic potential for a selection of peptides, both charged and uncharged, and other molecules of biological interest at the solvent accessible surface and beyond when compared with the full ab initio or density functional theory electrostatic potential. We also consider the ability of various point charge models to reproduce the full electrostatic potential and compare the results to our fragmentation electrostatic potentials with the latter being significantly superior. We demonstrate that our fragmentation approach can be readily applied to very large systems and provide the fragmentation electrostatic potential for the neuraminidase tetramer (ca. 24,000 atom system) at the MP2/6-311(+)G(2d,p) level. We also show that by using at least distributed monopoles, dipoles, and quadrupoles at atomic sites in the fragment molecules an essentially identical electrostatic potential to that given by the fragmentation electrostatic potential at and beyond the solvent accessible surface can be obtained.