Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.

Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity.

Enhanced Interleukin 6 Trans-Signaling Modulates Disease Process in Amyotrophic Lateral Sclerosis Mouse Models.

Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life.

An Entropy-Based Approach to Model Selection with Application to Single-Cell Time-Stamped Snapshot Data.

Recent single-cell experiments that measure copy numbers of over 40 proteins in individual cells at different time points [time-stamped snapshot (TSS) data] exhibit cell-to-cell variability. Because the same cells cannot be tracked over time, TSS data provide key information about the time-evolution of protein abundances that could yield mechanisms that underlie signaling kinetics. We recently developed a generalized method of moments (GMM) based approach that estimates parameters of mechanistic models using TSS data.

A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types.

Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. Currently, the complexity of these effector-target interactions and the donor-to-donor variations in NK cell receptor (NKR) repertoire require functional assays to be performed experimentally for each manufactured CAR-NK cell product and target combination. Here, we developed a computational mechanistic multiscale model which considers heterogenous expression of CARs, NKRs, adhesion receptors and their cognate ligands, signal transduction, and NK cell-target cell population kinetics.

Preliminary studies for the standardization of a pXRF analyzer ICP-OES for the accurate quantification of Pb in new paint.

Determining lead (Pb) concentrations in new paints using spectroscopic methods such as Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) requires technical expertise, consumables, equipment for method preparation, and instrumentation that can be cost prohibitive and difficult to maintain in low and middle-income countries (LMICs). Although portable X-ray Fluorescence (pXRF) analyzers are less expensive and simple to operate, their inaccuracy has limited their use to screening for the analysis of Pb in new, dried paint. To determine the limits of pXRF analyzers, new paint samples were purchased, dried, homogenized, and analyzed pXRF and ICP-OES.