The sound of an axon's growth

Axons are linear processes of nerve cells that can range from a few tens of micrometers up to meters in length. In addition to external cues, the length of an axon is also regulated by unknown internal mechanisms. Molecular motors have been suggested to generate oscillations with an axon length-dependent frequency that could be used to measure an axon's extension. Here, we present a mechanism that depends on the spectral decomposition of the oscillatory signal to determine the axon length.Comment: 5 pages, 4 figure

Frontiers of Cancer Diagnostics: From Photoacoustic Chemical Imaging to Cellular Morphodynamics

While terrific progress has been made over the last century, cancer continues to be a prevalent, lethal disease and is responsible for millions of deaths each year. The advent of personalized medicine has brought great strides in the treatment of cancer, as clinicians are able to select therapeutic courses that have been tailored to patients specific set of biomarkers. This selection, in principle, maximizes the chances of cancer remission while minimizing overall patient harm. In this spirit, we have focused on developing diagnostic techniques for two separate cancer biomarkers: tumor potassium concentration, and cell morphology. We first developed an ionophore-based potassium sensing nanoparticle. The sensor works on the principle of Donnan exclusion in which the overall charge of the carrier remains constant. The hydrophobic interior of the nanoparticle holds a pH-sensitive dye and a potassium ionophore. As the potassium concentrations rise, the ionophore chelates potassium from the solution which results in a proton being removed from the pH dye to maintain charge neutrality. The deprotonation event can be calibrated for quantitative measurement and this sensor was developed for use in diverse imaging modes, which include UV-VIS absorption, fluorescence, and photoacoustics. At physiological pH and in the presence of interfering ions, we were able to quantitatively measure potassium concentrations using each of these readouts. We modified the potassium sensor to enable in vivo measurements of potassium. This formulation makes use of a solvatochromic dye that transitions from the particle's interior to its surface as potassium is chelated, and thus avoids inherent pH-cross sensitivity. Using photoacoustic chemical imaging, we are able to quantitatively measure the potassium concentration in the tumor microenvironment. As predicted, it was shown that the TME is hyperkalemic, having a potassium concentration of 29mM. The results of the in vivo photoacoustic analysis were verified with ICP-MS measurements of TME potassium. Finally, we combined cell magneto-rotation and machine learning to develop a technique to measure the metastatic potential of a cancer cell population. This technique aims at avoiding the use of expensive and difficult to produce biological labels. By magnetically activating cells, we are able to suspend them in an oscillating magnetic field where they are free to explore their morphological shape space. By collecting fluorescence images of these cells, we are able to train a classifier to recognize cells of a given type. A proof of concept for the technique is provided here, where MCF-7 and MDA-MB-231 cells, both breast cancer but of different metastatic potential, were classified. A random forest classifier trained on cell images was able to correctly identify the cell type with 86.9% accuracy.PHDBiophysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163147/1/folzja_1.pd

The Land Use and Rapid Transportation Nexus in the Massachusetts Bay

ABSTRACT Throughout the last several decades a growing emphasis has been placed on creating sustainable places through innovative planning practices. Urban designers, researchers, planners, and policy makers have continuously examined the land use transportation nexus in order to develop methods to efficiently guide transit funding to encourage alternate modes of travel. The United States is in the middle of a paradigm shift in generational behaviors. Baby boomers are downsizing and according to the Urban Land Institute are looking for more location-efficient residences. Similarly, Generation Y\u27s attitudes are focused on living and working in close proximity. They are also waiting longer to obtain driver\u27s licenses and are instead looking for alternate modes of travel. This study looks at the Massachusetts Bay Transportation Authority\u27s rapid transit system through the scope of a linear regression analysis using 2010 rapid transit ridership data, 2010 Census data, 2006-2009 American Community Survey estimates, and 2011 employment data. This thesis examines previously researched themes and provides a new look at the transportation / land use nexus. It concludes that neither an increase in population density nor an increase in job density increase transit ridership. Instead, the physical built environment has the most influence over transit ridership in the Massachusetts Bay. When streets are dense and highly connected, access to transit is more convenient, causing people\u27s mode choice to shift from single-occupancy vehicles. Governing bodies and transit agencies in the Massachusetts\u27 Bay should create a close collaboration between municipalities, counties, and transit agencies if the MBTA wants to increase ridership levels on their rapid transit system. Land development regulations and zoning ordnances should encourage dense, well-connected streets and a high degree of land use mixing in areas where transit investments are likely to occur