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Biology subjects

Yim, M.

Publications and source records attributed to Yim, M..

4 recordsLinked to original sources

A repository of Ogden syndrome (NAA10) and NAA15 patient derived iPSC lines and isogenic pairs by X-chromosome screening and genome-editing.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, NAA10, encodes the enzyme NAA10, as the catalytic subunit for the N-terminal acetyltransferase A (NatA) complex, including the accessory protein, NAA15. The first human disease directly involving NAA10 was discovered in 2011, and it was named Ogden syndrome (OS), after the location of the first affected family residing in Ogden, Utah, USA. Since that time, other variants have been found in NAA10 and NAA15. Here we describe the generation of 31 iPSC lines, with 16 from females and 15 from males. This cohort includes CRISPR-mediated correction to the wild-type genotype in 4 male lines, along with editing one female line to generate homozygous wild-type or mutant clones. Following the monoclonalizaiton and screening for X-chromosome activation status in female lines, 3 additional pairs of female lines, in which either the wild type allele is on the active X chromosome (Xa) or the pathogenic variant allele is on Xa, have been generated. Subsets of this cohort have been successfully used to make cardiomyocytes and neural progenitor cells (NPCs). These cell lines are made available to the community via the NYSCF Repository.

genetics↗

Steerable Tape-Spring Needle for Autonomous Sharp Turns Through Tissue

Steerable needles offer a minimally invasive method to deliver treatment to hard-to-reach tissue regions. We introduce a new class of tape-spring steerable needles capable of sharp turns ranging from 15 to 150 degrees with a turn radius as low as 3mm, which minimizes surrounding tissue damage. In this work, we derive and experimentally validate a geometric model for our steerable needle design. We evaluate both manual and robotic steering of the needle along a Dubins path in 7 kPa and 13 kPa tissue phantoms, simulating our target clinical application in healthy and unhealthy liver tissue. We conduct experiments to measure needle robustness to stiffness transitions between non-homogeneous tissues. We demonstrate progress towards clinical use with needle tip tracking via ultrasound imaging, navigation around anatomical obstacles, and integration with a robotic autonomous steering system.

bioengineering↗

Grid Cell Firing Patterns Maintain their Hexagonal Firing Patterns on a Circular Track

In an open two-dimensional environment, grid cells in the medial entorhinal cortex are known to be active in multiple locations, displaying a striking periodic hexagonal firing pattern covering the entire space. Both modeling and experimental data suggest that such periodic spatial representations may emerge from a continuous attractor network. According to this theory, grid cell activity in any stable 1D environment is a slice through an underlying 2D hexagonal pattern, which is supported by some experimental studies but challenged by others. Grid cells are believed to play a fundamental role in path integration, and so understanding their behavior in various environments is crucial for understanding the flow of information through the entorhinal-hippocampal system. To this end, we analyzed the activity of grid cells when rats traversed a circular track. A previous study involving this data set analyzed individual grid cell activity patterns separately, but we found that individual grid cells do not provide sufficient data for determining the under-lying spatial activity pattern. To circumvent this, we compute the population autocorrelation, which pools together population responses from all grid cells within the same module. This novel approach recovers the underlying six-peak hexagonal pattern that was not observable in the individual autocorrelations. We also use the population autocorrelation to infer the spacing and orientation of the population lattice, revealing how the lattice differs across environments. Furthermore, the population autocorrelation of the linearized track reveals that at the level of the population, grid cells have an allocentric code for space. These results are strong support for the attractor network theory for grid cells, and our novel approach can be used to analyze grid cell activity in any undersampled environment.

neuroscience↗

A Tape Spring Steerable Needle Capable of Sharp Turns

ObjectiveTo make steerable needles more effective, researchers have been trying to minimize turning radius, develop mechanics-based models, and simplify control. This paper introduces a novel cable-driven steerable needle that has a 3mm turning radius based on tape spring mechanics, which sets a new minimum turn radius in stiffness-matched tissue models. Methods: We characterize the turn radius and the forces that affect control and performance and create predictive models to estimate required insertion forces and maximum insertion depth. Finally, we demonstrate the performance of a task outside the capabilities of a conventional needle. Results: Minimal force is required to maintain bends, allowing surrounding tissue to fix them in place, and minimal energy is required to propagate bends, allowing the device to navigate easily through various tissue phantoms. The turn radius of the device is independent of surrounding tissue stiffness, making for simple and precise control. We show that all aspects of performance depend on minimizing the tip cutting force. Under ultrasound guidance, we successfully navigate into and then follow a deep blood vessel model at a steep angle of approach. Conclusion: This design allows the system to accurately control the direction of the device while maintaining a smaller turn radius than other steerable needles, providing the potential to broaden access to challenging targets in patients.

bioengineering↗