How Well Can We Infer Selection Benefits and Mutation Rates from Allele Frequencies?

Experimentalists observe allele frequency distributions and try to infer mutation rates and selection coefficients. How easy is this? We calculate limits to their ability in the context of the Wright-Fisher model by first finding the maximal amount of information that can be acquired using allele frequencies about the mutation rate and selection coefficient- at least 2 bits per allele- and then by finding how the organisms would have shaped their mutation rates and selection coefficients so as to maximize the information transfer.

A novel contact-free atrial fibrillation monitor: a pilot study.

Aims: Atrial fibrillation (AF) is a major cause of morbidity and mortality. Current guidelines support performing electrocardiogram (ECG) screenings to spot AF in high-risk patients. The purpose of this study was to validate a new algorithm aimed to identify AF in patients measured with a recent FDA-cleared contact-free optical device.

Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells.

Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.

CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies.

Purpose: To assess the potential for CUE-101, a novel therapeutic fusion protein, to selectively activate and expand HPV16 E7-specific CD8 T cells as an off-the shelf therapy for the treatment of HPV16-driven tumors, including head and neck squamous cell carcinoma (HNSCC), cervical, and anal cancers.

Experimental Design: CUE-101 is an Fc fusion protein composed of a human leukocyte antigen (HLA) complex, an HPV16 E7 peptide epitope, reduced affinity human IL2 molecules, and an effector attenuated human IgG1 Fc domain. Human E7-specific T cells and human peripheral blood mononuclear cells (PBMC) were tested to demonstrate cellular activity and specificity of CUE-101, whereas activity of CUE-101 was assessed in HLA-A2 transgenic mice.