Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells

A Groupoid Construction of Functional Integrals: Brownian Motion and Some TQFTs

We formalize Feynman's construction of the quantum mechanical path integral. To do this, we shift the emphasis in differential geometry from the tangent bundle onto the pair groupoid. This allows us to use the van Est map and the piecewise linear structure of manifolds to develop a coordinate-free, partition of unity-free approach to integration of differential forms, etc. This framework makes sense for any field theory valued in a Lie algebroid. We apply it to define the Wiener measure, stochastic integrals and other observables in a coordinate-free way. We use it to reconstruct Chern-Simons with finite gauge group and to obtain some non-perturbative deformation quantizations via the Poisson sigma model on a disk

A Mathematical Definition of Path Integrals on Symplectic Manifolds

We give a mathematical definition of some path integrals, emphasizing those relevant to the quantization of symplectic manifolds (and more generally, Poisson manifolds) \unicode{x2013} in particular, the coherent state path integral. We show that K\"{a}hler manifolds provide many computable examples and we emphasize those whose Bergman kernel is constant along the diagonal.Comment: 23 pages. Some edits to examples, exposition, references in second versio

Geometric Quantization Without Polarizations

We derive the quantization map in geometric quantization of symplectic manifolds via the Poisson sigma model. This gives a polarization-free (path integral) definition of quantization which pieces together most known quantization schemes. We explain how this allows Schur's lemma to address the invariance of polarization problem. We compute this quantization map for the torus and obtain the noncommutative torus and its standard irreducible representation.Comment: 20 pages. Fixed typos, minor edits to exposition and reference

A Derivation of Geometric Quantization via Feynman's Path Integral on Phase Space

We derive the geometric quantization program of symplectic manifolds, in the sense of both Kostant-Souriau and Weinstein, from Feynman's path integral formulation on phase space. The state space we use contains states with negative norm and polarized sections determine a Hilbert space. We discuss ambiguities in the definition of path integrals arising from the distinct Riemann sum prescriptions and its consequence on the quantization of symplectomorphisms.Comment: 10 pages plus appendix and reference

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface

A Groupoid Approach to the Riemann Integral (and Path Integral Quantization of the Poisson Sigma Model)

We use groupoids and the van Est map to define Riemann sums on compact manifolds (with boundary), in a coordinate-free way. These Riemann sums converge to the usual integral after taking a limit over all triangulations of the manifold. We show that the van Est map determines the n-jet of antisymmetric n-cochains. We discuss using this Riemann sum construction to put the Poisson sigma model on a lattice

Sales Forecasting in the Railroad Industry

C. L. Lackman is Professor of Economics at North Carolina Agricultural and Technical State University in Greensboro