Reliability at Scale: Pushing the Boundaries of Reliability and Quality at the Frontiers of Compute

Silicon Lifecycle Management: Increasing Semiconductor Predictability in an Unpredictable World

The Loyola University Chicago Department of Physics offers a B.S. in Biophysics program that consists of a balanced blend of biology, chemistry, and physics coursework. As a capstone experience, students must complete an upper-level biophysics course. Although the course has a a significant lecture component with a focus on molecular and cellular biophysics as well as biomechanics, the aim of the course is for students to engage in professional science activities. Classroom activities include interpreting results from journal articles, writing an NIH-style research proposal on an instructor-approved topic with peer reviews, and completing an experimental project. I will present an overview of the course, its activities, and challenges. Students are also encouraged to participate in faculty research, and my undergraduate-only lab has several student researchers conducting experiments in single-molecule DNA microscopy. I will also discuss how the lab recruits students, trains them for research, and mentors their progress.

Transitioning Students from Learning Biophysics to Doing Biophysics

A new active-learning pedagogy is presented that includes computation as a central theme. The approach starts with the "marble game", a kinetic Monte Carlo simulation of diffusion. Students first learn how to play the game by hand and then implement it in Excel to discover that Fick's law of diffusion can be explained by random jumping between two boxes. In a guided-inquiry environment, students apply the same techniques to drug elimination, radioactive decay, osmosis, ligand binding, enzyme kinetics, and ion channel permeation. Students discover for themselves the consequences and significance of model assumptions by reading and interpreting graphs, and by comparing model predictions with real data using linear regression and non-linear least-squares fits. The pedagogical objective is for students to discover for themselves that science is an evidence-based endeavor with testable hypotheses that are supported by experiment.

Biophysics in the Undergraduate Curriculum

The biological cell exhibits a fantastic range of behaviors, but ultimately these are governed by a handful of physical and chemical principles. Here we explore simple theory, known for decades and based on the simple thermodynamics of mixtures of ideal gases, which illuminates several key functions performed within the cell. Our focus is the free-energy-driven import and export of molecules, such as nutrients and other vital compounds, via transporter proteins. Complementary to a thermodynamic picture is a description of transporters via "mass-action" chemical kinetics, which lends further insights into biological machinery and free energy use. Both thermodynamic and kinetic descriptions can shed light on the fundamental non-equilibrium aspects of transport. Our biochemical-physics discussion will remain agnostic to chemical details.

Key biology you should have learned in physics class

We first phrase a boundary-value problem for a dense, steady, fully-developed, gravitational flow of identical inelastic spheres over in inclined bumpy base in the absence of sidewalls. We then obtain approximate analytical solutions for the profiles of the solid volume fraction, the strength of the velocity fluctuations, and the mean velocity of the flow. We compare these with those obtained in numerical solutions of the exact equations.

Analytical solutions for dense, inclined, granular flow over a rigid, bumpy base

Granular assemblies can experience complex failure patterns along a given loading path, with adistribution of ephemeral inertial events marked by local outbursts in kinetic energy. However, investigatingsuch mechanisms appears to be necessary to understand how a certain failure mode develops in a granularmaterial. Using a discrete element method, this study highlights several microstructure reorganizationsbefore the specimen reaches a proper failure state. Meso structures have proven to be efficient to understand the elementary mechanisms responsible for these outbursts in kinetic energy. Strain–like and stress-like quantities are thus defined at a mesoscale and they are used to characterize the nucleation and propagation of these local microstructural events.

Mesoscale inertial transition in granular materials

Multiscale modeling of granular media for geomechanics and beyond

Predicting avalanches in granular materials from 'vibrational' modes

Development of portable X-ray fluorescence devices has made it easier to quickly assess trace elements such as zinc in human tissue. Zinc deficiency can have serious implications on growth and development of the human body. From recent studies zinc content in nail clippings has been suggested to be an effective biomarker for zinc status. In this study, a simulation approach was used to investigate the use of a portable X-ray fluorescence system for detecting the variation of zinc signal with respect to nail thickness and was compared with the experimental results. The portable X-ray device was modelled using the available information from the manufacturer using the TOPAS Monte Carlo code (Geant4 simulation software).The simulations were carried out for varying nail phantom thickness (0.2 mm – 1.2 mm) with concentration of 1000 ppm zinc. Each simulation was run for 10^9 histories and the statistical uncertainty was less than 3.5%. The obtained energy spectra from different measurements were analyzed and three different normalization techniques (Coherent, Compton and Entire) spectrum were investigated to account for the variation of sample interrogated by the X-ray beam. Close agreement between simulation and experimental trends were observed indicating successful benchmarking of the simulation. Compton and Coherent normalization followed a slightly negative trend. One other important observation was coherent normalization can be a robust normalization procedure to improve the accuracy of elemental quantification in order to reduce the variability in nail thickness by ~8%. Overall the simulation approach can provide additional insights into elemental analysis in keratin based nail phantoms.

Investigating normalizing methods for X-ray fluorescence measurements of Zinc in nail clippings using TOPAS Monte Carlo code

From cytoskeleton to centriole, we investigate the photonic inner workings of the living cell. The cytoskeleton provides the structural organization of the cell, as the supporting architecture for all known forms of life. A major structural unit of this architecture is the cellular “microtubule,” a hollow tubular body composed of individual units of the protein “tubulin” organized in an array of spiral-shaped components. Recently, it was proposed that microtubules may exhibit useful photonic properties, as well as a myriad of known structural features. In this work, we explore the role that photonic super-radiance may play in facilitating excitonic transport and communication within the cellular architecture, from the cytoskeleton to the eukaryotic centriole—and beyond.

Photonic Cooperativity and Coherence in Tubulin Architectures

Morphogens (often acting as transcription activators or repressors) govern pattern formation and cell differentiation during early embryogenesis. Abnormal distributions of morphogens can result in developmental defects or even death. Oftentimes, thresholds of concentrations of morphogens behave like an ON/OFF switch for the activation or repression of downstream genes. Thus accurate measurements of morphogen concentration and mobility in space and time can help tackle the puzzle of how exactly cascades of hundreds of morphogens coordinate their targets precisely and promptly amidst crowded and complicated cellular environments. 

In principle, Fluorescence Correlation Spectroscopy (FCS) allow for accurate measurements of both protein dynamics and concentration. Here, we demonstrate how to use FCS and confocal imaging to achieve extremely low (~ nM) concentration measurements in live Drosophila embryos expressing recombinant fluorescent morphogens, by carefully taking account background noise and photobleaching effects. The dynamics of both an activator and a repressor morphogens were further studied using FCS and Fluorescence Recovery After Photobleaching. We found that both type of morphogens are very mobile in nuclei, explaining how that are able to turn on or off gene expression in only a few minutes.

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Reliability at Scale: Pushing the Boundaries of Reliability and Quality at the Frontiers of Compute

Silicon Lifecycle Management: Increasing Semiconductor Predictability in an Unpredictable World

Transitioning Students from Learning Biophysics to Doing Biophysics

Biophysics in the Undergraduate Curriculum

Key biology you should have learned in physics class

Analytical solutions for dense, inclined, granular flow over a rigid, bumpy base

Mesoscale inertial transition in granular materials

Multiscale modeling of granular media for geomechanics and beyond

Predicting avalanches in granular materials from 'vibrational' modes

Investigating normalizing methods for X-ray fluorescence measurements of Zinc in nail clippings using TOPAS Monte Carlo code

Photonic Cooperativity and Coherence in Tubulin Architectures

Concentration and Mobility of Activator and Repressor Morphogens in live early Drosophila Embryos

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