Application of Artificial Intelligence/Machine Vision & Learning for the Development of a Live Single-cell Phenotypic Biomarker Test to Predict Prostate Cancer Tumor Aggressiveness.

To the usefulness and applications of machine vision (MV) and machine learning (ML) techniques that have been used to develop a single cell-based phenotypic (live and fixed biomarkers) platform that correlates with tumor biological aggressiveness and risk stratification, 100 fresh prostate samples were acquired, and areas of prostate cancer were determined by post-surgery pathology reports logged by an independent pathologist. The prostate samples were dissociated into single-cell suspensions in the presence of an extracellular matrix formulation. These samples were analyzed via live-cell microscopy.

Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism.

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein.

Characterizing Multiscale Mechanical Properties of Brain Tissue Using Atomic Force Microscopy, Impact Indentation, and Rheometry.

To design and engineer materials inspired by the properties of the brain, whether for mechanical simulants or for tissue regeneration studies, the brain tissue itself must be well characterized at various length and time scales. Like many biological tissues, brain tissue exhibits a complex, hierarchical structure. However, in contrast to most other tissues, brain is of very low mechanical stiffness, with Young's elastic moduli E on the order of 100s of Pa.

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance.

Immune cell trafficking requires the frequent breaching of the endothelial barrier either directly through individual cells ('transcellular' route) or through the inter-endothelial junctions ('paracellular' route). What determines the loci or route of breaching events is an open question with important implications for overall barrier regulation. We hypothesized that basic biomechanical properties of the endothelium might serve as crucial determinants of this process.

Onset of heterogeneity in culture-expanded bone marrow stromal cells.

Inconsistencies among in vitro and in vivo experiments using adult mesenchymal stem cells (MSCs) confound development of therapeutic, regenerative medicine applications, and in vitro expansion is typically required to achieve sufficient cell numbers for basic research or clinical trials. Though heterogeneity in both morphology and differentiation capacity of culture-expanded cells is noted, sources and consequences are not well understood. Here, we endeavored to observe the onset of population heterogeneity by conducting long-term continuous in vitro observation of human adult bone marrow stromal cell (BMSC) populations, a subset of which has been shown to be stem cells (also known as bone marrow-derived MSCs).

Directional cell migration in an extracellular pH gradient: a model study with an engineered cell line and primary microvascular endothelial cells.

Extracellular pH (pH(e)) gradients are characteristic of tumor and wound environments. Cell migration in these environments is critical to tumor progression and wound healing. While it has been shown previously that cell migration can be modulated in conditions of spatially invariant acidic pH(e) due to acid-induced activation of cell surface integrin receptors, the effects of pH(e) gradients on cell migration remain unknown.

Shear-stabilized rolling behavior of E. coli examined with simulations.

Escherichia coli exhibit both shear-stabilized rolling and a transition to stationary adhesion while adhering in fluid flow. Understanding the mechanism by which this shear-enhanced adhesion occurs is an important step in understanding bacterial pathogenesis. In this work, simulations are used to investigate the relative contributions of fimbrial deformation and bond transitions to the rolling and stationary adhesion of E.