Quicklists
public 59:29

Louis Fostier : A model of oocyte population dynamics for fish oogenesis

  -   Mathematical Biology ( 60 Views )

We introduce and analyze a size-structured oocyte population model, with non local nonlinearities on recruitment, growth and mortality rates to take into account interactions between cells. We pay special attention to the form of the recruitment term, and its influence on the asymptotic behavior of the cell population.
This model is well-suited for representing oocyte population dynamics within the fish ovary. The nonlocal nonlinearities enable us to capture the diverse feedback mechanisms acting on the growth of oocytes of varying sizes and on the recruitment of new oocytes.
We firstly investigate the existence and uniqueness of global bounded solutions by transforming the partial differential equation into an equivalent system of integral equations, which can be solved using the Contraction Mapping Principle.
In a second step, we investigate the asymptotic behavior of the model. Under an additional assumption regarding the form of the growth rate, we can, with the use of a classical time-scaling transformation, reduce the study to that of a equation with linear growth speed and nonlinear inflow boundary condition. Using arguments from the theory of abstract semilinear Cauchy problems, we investigate the local stability of stationary solutions of this equation by reducing it to a characteristic equation involving the eigenvalues of the linearized problem around equilibrium states.
When the mortality rate is zero, the study of existence and stability of stationary solutions is simplified. Explicit calculations can be carried out in certain interesting cases.

public 53:20

Dean Bottino : Evaluating Strategies for Overcoming Rituximab (R) Resistance Using a Quantitative Systems Pharmacology (QSP) model of Antibody-Dependent Cell-mediated Cytotoxicity & Phagocytosis (ADCC & ADCP): An Academic/Industrial Collaboration

  -   Mathematical Biology ( 70 Views )

Despite the impressive performance of rituximab (R) containing regimens like R-CHOP in CD20+ Non-Hodgkin’s Lymphoma (NHL), 30-60% of R-naïve NHL patients are estimated to be resistant, and approximately 60% of those patients will not respond to subsequent single agent R treatment. Given that antibody dependent cell mediated cytotoxicity (ADCC) and phagocytosis (ADCP) are thought to be the major mechanisms of action of Rituximab, increasing the activation levels of natural killer (NK) and macrophage (MP) cells may be one strategy for overcoming R resistance.

During (and after) the Fields Institute Industrial Problem Solving Workshop in August 2019, academic participants and industry mentors developed and calibrated to literature data a quantitative systems pharmacology (QSP) model of ADCC/ADCP to interrogate which mechanisms of R resistance could be overcome by increased NK or MP activation, and how much effector cell activation would be required to overcome a given degree and mechanism of R resistance.

This work was motivated by a real-world pharmaceutical drug development question, and the academic-industry interactions during and after the workshop resulted in sharknado plots as well as a published QSP model (presented at American Association of Cancer Research Annual Meeting, 2021) that was able to address some of the key questions around overcoming R resistance. The published model was then incorporated into an in-house QSP model supporting the development of a Takeda investigational drug which is being developed to restore R sensitivity in an R-resistant patient population.

public 51:31

Punit Gandhi : Conceptual modeling of dryland vegetation patterns across timescales

  -   Mathematical Biology ( 86 Views )

Strikingly regular, large-scale patterns of vegetation growth were first documented by aerial photography in the Horn of Africa circa 1950 and are now known to exist in drylands across the globe. The patterns often appear on very gently sloped terrain as bands of dense vegetation alternating with bare soil, and models suggest that they may be a strategy for maximizing usage of the limited water available. A particular challenge for modeling these patterns is appropriately resolving fast processes such as surface water flow during rainstorms while still being able to capture slow dynamics such as the uphill migration of the vegetation bands, which has been observed to occur on the scale of a band width per century. We propose a pulsed-precipitation model that treats rainstorms as instantaneous kicks to the soil water as it interacts with vegetation on the timescale of plant growth. We use a stochastic rainfall model with the influence of fast storm-level hydrology captured by the spatial distribution of the soil water kicks. The model allows for predictions about the influence of storm characteristics on the large-scale patterns. Analysis and simulations suggest that the distance water travels on the surface before infiltrating into the soil during a typical storm plays a key role in determining the spacing between the bands.

public 01:14:53

Stephan Huckemann : Statistical challenges in shape prediction of biomolecules

  -   Mathematical Biology ( 171 Views )

The three-dimensional higher-order structure of biomolecules determines their functionality. While assessing primary structure is fairly easily accessible, reconstruction of higher order structure is costly. It often requires elaborate correction of atomic clashes, frequently not fully successful. Using RNA data, we describe a purely statistical method, learning error correction, drawing power from a two-scale approach. Our microscopic scale describes single suites by dihedral angles of individual atom bonds; here, addressing the challenge of torus principal component analysis (PCA) leads to a fundamentally new approach to PCA building on principal nested spheres by Jung et al. (2012). Based on an observed relationship with a mesoscopic scale, landmarks describing several suites, we use Fréchet means for angular shape and size-and-shape, correcting within-suite-backbone-to-backbone clashes. We validate this method by comparison to reconstructions obtained from simulations approximating biophysical chemistry and illustrate its power by the RNA example of SARS-CoV-2.

This is joint work with Benjamin Eltzner, Kanti V. Mardia and Henrik Wiechers.

Literature:

Eltzner, B., Huckemann, S. F., Mardia, K. V. (2018): Torus principal component analysis with applications to RNA structure. Ann. Appl. Statist. 12(2), 1332?1359.

Jung, S., Dryden, I. L., Marron, J. S. (2012): Analysis of principal nested spheres. Biometrika, 99 (3), 551-568

Mardia, K. V., Wiechers, H., Eltzner, B., Huckemann, S. F. (2022). Principal component analysis and clustering on manifolds. Journal of Multivariate Analysis, 188, 104862, https://www.sciencedirect.com/science/article/pii/S0047259X21001408

Wiechers, H., Eltzner, B., Mardia, K. V., Huckemann, S. F. (2021). Learning torus PCA based classification for multiscale RNA backbone structure correction with application to SARS-CoV-2. To appear in the Journal of the Royal Statistical Society, Series C, bioRxiv https://doi.org/10.1101/2021.08.06.455406

public 01:34:56

Casey Diekman : Data Assimilation and Dynamical Systems Analysis of Circadian Rhythmicity and Entrainment

  -   Mathematical Biology ( 122 Views )

Circadian rhythms are biological oscillations that align our physiology and behavior with the 24-hour environmental cycles conferred by the Earth’s rotation. In this talk, I will discuss two projects that focus on circadian clock cells in the brain and the entrainment of circadian rhythms to the light-dark cycle. Most of what we know about the electrical activity of circadian clock neurons comes from studies of nocturnal (night-active) rodents, hindering the translation of this knowledge to diurnal (day-active) humans. In the first part of the talk, we use data assimilation and patch-clamp recordings from the diurnal rodent Rhabdomys pumilio to build the first mathematical models of the electrophysiology of circadian neurons in a day-active species. We find that the electrical activity of circadian neurons is similar overall between nocturnal and diurnal rodents but that there are some interesting differences in their responses to inhibition. In the second part of the talk, we use tools from dynamical systems theory to study the reentrainment of a model of the human circadian pacemaker following perturbations that simulate jet lag. We show that the reentrainment dynamics are organized by invariant manifolds of fixed points of a 24-hour stroboscopic map and use these manifolds to explain a rapid reentrainment phenomenon that occurs under certain jet lag scenarios.