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Archive : Applied Mathematics and Mathematical Medicine and Biology Seminar

 

 

Jason Gleghorn, University of Delaware, Department of BioengineeringJason Gleghorn, University of Delaware, Department of BioengineeringEwing 226<div class="WordSection1"><div><p class="MsoNormal" style="">Title: Tissue origami: physical mechanisms that drive branching morphogenesis of developing organs</p><p class="MsoNormal" style="">Abstract: Branching morphogenesis is a developmental program used by many organs, including the lung, kidney, prostate, and mammary gland, to create ramified networks of epithelial tubes that support the flow of fluid and air.  Development of the lung is dynamic, highly regulated, and stereotyped, leading to an airway architecture that is conserved within a given species and critical for survival. Interestingly, although the architecture of the airways is optimized for efficient conduction of air, development occurs with a fluid-filled lumen. Whereas almost all contemporary studies focus on the molecular and genetic programs active during branching morphogenesis of the lung, clinical observations and large animal models suggest a critical role for the (dynamic) regulation of mechanical forces, e.g. transmural pressure, in the developing lung. To investigate the role of transmural pressure in branching morphogenesis, I discuss the development of a microfluidic device to culture and apply dynamically-controlled transmural pressures within murine embryonic whole lung explants. This new approach permits the branching process to be imaged dynamically at multiple length and time scales under defined mechanical conditions over days of organ development. Using this microfluidic device along with newly developed measurement techniques and quantitative frameworks to describe the airway architecture, I discuss how lumenal fluid flows, generated by pressure-dependent airway smooth muscle contractions, drive branching morphogenesis. Together, my results demonstrate a novel physical mechanism through which lung branching morphogenesis – the temporal and spatial regulation of billions of individual cells - is mechanically regulated in normal development. These studies 1) suggest that lumenal fluid forces may be critical for sculpting the airway architecture, ultimately leading to enhanced convection of air through the mature airway tree and 2) point to additional studies to determine how mechanical forces integrate into the developing tissues.</p></div></div>11/15/2016 8:30:00 PM11/15/2016 9:30:00 PMFalse
Richard Spencer (NIH) Richard Spencer (NIH)Ewg 336<div class="WordSection1"><div><p class="MsoNormal">Title: Linear and Nonlinear Inverse Problems Arising from Magnetic Resonance Relaxometry Analysis of Macromolecular Components in Tissue <br><br>Abstract: Fourier transform nuclear magnetic resonance spectroscopy (FT-NMR) has been extraordinarily successful for characterizing samples with molecular components that resonate at different frequencies in an external magnetic field. In FT-NMR, molecular components can be obtained from the observed data by a Fourier transform. Unfortunately, there are many examples in which the NMR signal is comprised of components of equal frequency, so that the Fourier transform cannot directly resolve them. An important example is studies of tissue water, the largest component of biological tissues; the differences in resonance frequency of the water within different tissue compartments are small in comparison to spectral line widths, rendering these components of the water signal indistinguishable. However, when <br>components exhibit exponential decay with different relaxation time constants, the inverse Laplace transform (ILT) may be used instead of the FT to resolve and quantify them. Unlike the FT, the ILT is an ill-posed problem so that this procedure is fraught with difficulty. We have found that the stability of the regularized ILT is improved in higher dimensions (e.g. N = 2 or 3), leading to the potential for much improved quantitative tissue analysis in certain circumstances. The lengthy experimental times required for higher-dimensional relaxometry can be partially ameliorated by the use of compressed sensing. Finally, these time-consuming approaches have limitations for high-resolution macromolecular mapping in human subjects, so that we have investigated more complex signal models as well. These have been applied to myelin water mapping in brain and proteoglycan mapping in cartilage in human subjects. We have found that a Bayesian approach to the nonlinear inverse problem of deriving parameter estimates in this setting provides a substantial improvement over conventional non-negative least squares analyses. </p></div></div>11/1/2016 7:30:00 PM11/1/2016 8:30:00 PMFalse
Joshua Schneider, UCLAJoshua Schneider, UCLAEwg 336 <div dir="LTR"><font face="Arial">Title:</font> <font face="Arial">On the Atomistic Underpinnings of the BCF Model of Crystal Growth</font></div> <div dir="LTR"><font face="Arial">Abstract:</font> <font face="Arial">Epitaxial growth of crystalline materials is a technique used in </font></div> <div dir="LTR"><font face="Arial">the fabrication of semiconductors and other nanodevices. One notable model </font></div> <div dir="LTR"><font face="Arial">of the growth process, proposed by Burton, Cabrera, and Frank (BCF) in </font></div> <div dir="LTR"><font face="Arial">1951, describes the motion of defects resembling steps on the surface of a </font></div> <div dir="LTR"><font face="Arial">crystal. This model includes (i) a diffusion equation for the density of </font></div> <div dir="LTR"><font face="Arial">adsorbed atoms (adatoms) on the surface, (ii) Robin boundary conditions for </font></div> <div dir="LTR"><font face="Arial">the mass flux of adatoms at step edges, and (iii) a step velocity law </font></div> <div dir="LTR"><font face="Arial">determined by mass conservation. In this work we show how (i)-(iii) emerge </font></div> <div dir="LTR"><font face="Arial">in the continuum limit of a discrete description of surface evolution. Our </font></div> <div dir="LTR"><font face="Arial">starting point is a kinetic, restricted solid-on-solid (KRSOS) model: A </font></div> <div dir="LTR"><font face="Arial">Markov process whose evolution is governed by a master equation. Using the </font></div> <div dir="LTR"><font face="Arial">master equation directly, we derive discrete equations of motion for </font></div> <div dir="LTR"><font face="Arial">averages over KRSOS microstates, and consider the limit of small lattice </font></div> <div dir="LTR"><font face="Arial">spacing. To recover the BCF model in this limit, we find estimates for </font></div> <div dir="LTR"><font face="Arial">*discrete </font></div> <div dir="LTR"><font face="Arial">correction terms* associated with KRSOS averages and deduce criteria under </font></div> <div dir="LTR"><font face="Arial">which they may be neglected. Complementing this result, we use kinetic </font></div> <div dir="LTR"><font face="Arial">Monte Carlo simulations to show that the BCF model may break down when such </font></div> <div dir="LTR"><font face="Arial">criteria are violated. To account for the full range of dynamics displayed </font></div> <div dir="LTR"><font face="Arial">by the KRSOS model, we propose a revised, BCF-like model including a </font></div> <div dir="LTR"><font face="Arial">*nonlinearity </font></div> <div dir="LTR"><font face="Arial">*in the boundary conditions at steps. Through analysis of an atomistic </font></div> <div dir="LTR"><font face="Arial">model, we determine the impact of microscale dynamics on a mesoscale </font></div> <div dir="LTR"><font face="Arial">description of crystal surface evolution.</font></div> 10/25/2016 7:30:00 PM10/25/2016 8:30:00 PMFalse
Muge Capan (Christiana Care Value Institute) Muge Capan (Christiana Care Value Institute)EWG 336<div class="WordSection1"><div><p class="MsoNormal" style="">Title: An Innovative Approach to Development and Implementation of Early Warning Systems Addressing Physiological Deterioration of Hospitalized Patients <br><br>Abstract: Early warning systems (EWS) are a critical tool to facilitate continuous awareness of patient health. Currently, the utility of clinical EWS is not fully realized due to undesirable performance characteristics that contribute to provider alarm fatigue. <br><br>This presentation will focus on our study with the goal of developing an EWS that combines physiologic measures and subjective assessments of a patient’s clinical status, using advanced analytics to develop threshold-based clinical recommendations. A case study will be presented to explore the application of the EWS on a new nurse rounding program. More specifically, high reliability organizations have a culture which involves a preoccupation with failure. A potential high reliability tool is a provider team that proactively rounds on patients attempting to identify signs of clinical deterioration rather than a delayed response as is common for many rapid response teams. However, in a resource constrained environment it is critical to understand how to best design and measure these efforts to ensure optimal care and safety. We iteratively developed and evaluated a new Proactive Rounding Process (PRP) conducted by nurses to accurately risk stratify patients, efficiently use resources and proactively provide care. Retrospective case-control evaluation with propensity score matched controls were used to measure and evaluate the impact of systematic changes on patient outcomes. Our implementation of a new PRP has resulted in enhance risk stratification and better targeting patients requiring an intervention. </p></div></div>10/18/2016 7:30:00 PM10/18/2016 8:30:00 PMFalse

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