Outside the world of mathematics it appears that math has remained a steady and consistent field since Newton and Leibniz discovered calculus in the 17th century. After all, 2 x 2 always equals 4 and the slope of a vertical line is always undefined. So how can mathematics really transform? In this month’s highlight article, the January Postdoc of the Month Winner, Dr. Brittany Fasy, describes her work in the new mathematical field of Topical Data Analysis (TDA). TDA is a unique combination of algebraic topology and pure mathematics that allows for topological organization of large data sets to identify areas of persistence and thus, relevance. Applications of TDA range from identifying areas of high human traffic for strategic advertising, to characterizing the organization of the universe, to diagnosing cancer.
Persistent homology is a widely used tool in Topological Data Analysis that encodes multi-scale topological information as a multi-set of points in the plane, called a persistence diagram. Each of these persistence points is associated with a lifetime (or persistence). Features with short lifetimes are informally considered to be topological noise, and those with a long lifetime are considered to be topological signal. We bring some statistical ideas to persistent homology in order to derive conï¬dence sets that allow us to separate topological signal from topological noise. We also apply statistical theory to other topological descriptors such as the persistence landscape or silhouette, rather than working with the original diagrams or data sets. We motivate this work with three applications.
Accurate diagnosis of most middle ear pathological conditions including otitis media remains challenging in a clinical setting. Standard ear evaluations are still performed primarily on the basis of human recognition of morphologic patterns in vivo using white light otoscope and suffer from significant observer variability providing minimal understanding of a disease’s underlying biochemistry. Owing to the biochemical specificity and multiplexing capability, spectroscopy-based chemical imaging has emerged as a promising tool for middle ear disease diagnosis in a real-time, label-free and non-destructive manner. Here, we critically review the spectroscopy-based approaches employed to study middle ear pathological conditions.
Alzheimer’s disease (AD) is a devastating illness with unknown etiology and no cure. The predominant model for studying AD has been transgenic mice with human mutant amyloid-ß (Aß) protein designed to reflect inherited familial forms of AD (fAD). However, this approach only reflects a small percentage of the AD population and has not lead to successful therapeutics. There is recent and compelling evidence that the Aß is not simply a misfolded protein that accumulates to eventual AD, but instead a protein with physiological roles that responds to several pathological contexts. If we better understand the contexts that stimulate Aß accumulation, and the character of its response, we can refocus research on targets upstream of Aß. In order to do this, the field needs models of late-onset AD (LOAD) that do not rely on human transgenes in mice. This perspective outlines models of contextually-driven Aß accumulation, animals with naturally elevated Aß and a potential human organ model that may be employed to better understand the role of Aß in AD.
In this discussion we present a course in cancer biology and therapeutics that we have taught for high school students the past five summers. Course content as well as data quantifying student learning are presented. Our hope is to provide guidance to those teaching similar courses or a template to teach the same course elsewhere.
One of the most influencing theories in numerical cognition proposes a specialized cognitive system for extracting number out of visual displays. This system has been suggested to map number onto a mental representation of space, the mental number line. While initially number extraction was said to occur independent of visual features, recent evidences challenge this view. After introducing the basics of numerical cognition, the current article will briefly outline this ongoing dispute based on literature coming from the line bisection task. Finally, directions for future research are proposed.
Ohio State University researchers have made a leap forward in disease research by creating an eraser sized human “brain” in a petri dish1. Although lacking a circulatory system their brain model includes spinal cord, cortex, midbrain, brain stem, and even the beginnings of an eye- aiding in the effectiveness of research on complex neurological disease. To create their new brain model, the researchers converted adult skin cells into pluripotent stem cells, which afforded the opportunity to build the multiple nervous cell types required for such a complex system. Having this tissue model will assist researchers in developing new disease models, and thus, facilitate the development of novel clinical interventions.
Recent studies have shown that mitochondria derived damage associated molecular pattern molecules (mtDAMP) are increased in the blood circulation of patients suffering from severe injuries and sepsis. DAMP’s (including mitochondrial DNA and proteins) are considered to be pro-inflammatory and one of the important mediators of ongoing systemic inflammation during sepsis. The mechanism of mtDAMP release during sepsis is currently enigmatic. In this regards, the recent paper by Kana et al.  in Autophagy shows that upon lipopolysaccharide stimulation of primary hepatic cells, active extracellular release of mtDAMP occurs through the exocytosis of autolysosomes. Inhibition of the autophagy process attenuated the mtDAMP release from the cells. These data demonstrate the active role of autophagy in secretion of cellular proteins from the cells during inflammatory conditions like sepsis. This paper provides important insight into the mechanism of sepsis induced mtDAMP release and provides background for future investigations.
Gene therapy to the gastrointestinal tract has remarkable potential for treating gastrointestinal disorders that currently lack effective treatments. Adeno-associated viral vectors (AAVs) have been extensively applied to the central nervous system, and have repeatedly demonstrated safety and efficacy in animal models. The enteric nervous system (ENS) represents a vast collection of neurons and glial cells that may also be subject to treatment by AAV, however little work has been conducted on AAV delivery to the ENS. Challenges for gastrointestinal gene therapy include identifying gene targets, optimizing gene delivery, and target cell selection. Researchers are now beginning to tackle the later of the two challenges with AAV, and the same AAV technology can be used to identify novel gene targets in the future. Continued efforts to understand AAV delivery and improve vector design are essential for therapeutic development. This review summarizes the current knowledge about AAV delivery to the ENS.
Acetate assimilation in C. reinhardtii leads to bicarbonate and CO2aq formation in heterotrophic growth condition. Bicarbonate and CO2aq thus formed under this condition remain in equilibrium with the action of carbonic anhydrases. Carbonic anhydrase catalyzes reversible hydration of carbon dioxide and dehydration of bicarbonate. In this article we report that the rapid exchange catalyzed by extracellular carbonic anhydrase causes a large magnetization (saturation) transfer effect on the 13C signal of bicarbonate at 161.01 ppm when the resonance of the carbon dioxide (aq) at 125.48 ppm is irradiated with RF pulses. In C. reinhardtii extracellular space the unidirectional, pseudo first-order rate constant of this exchange in the dehydration direction was determined to be 0.011 ± 0.005 sec-1. The presence of highly specific carbonic anhydrase inhibitor acetazolamide, was also shown to drastically attenuate the observed 13C magnetization transfer effect of the carbon dioxide–bicarbonate exchange in C. reinhardtii. We have demonstrated the utility of 13C saturation transfer for determining the exchange rate between bicarbonate and carbon dioxide catalyzed by extracellular carbonic anhydrase in C. reinhardtii extracellular space.This study for the first time reports the dehydration rate of bicarbonate to CO2 in live C. reinhardtii cells.