James Keener : Flexing your Protein muscles: How to Pull with a Burning Rope
- Mathematical Biology ( 727 Views )The segregation of chromosomes during cell division is accomplished by kinetochore machinery that uses depolymerizing microtubules to pull the chromosomes to opposite poles of the dividing cell. While much is known about molecular motors that pull by walking or push by polymerizing, the mechanism of how a pulling force can be achieved by depolymerization is still unresolved. In this talk, I will describe a new model for the depolymerization motor that is used by eukaryotic cells to segregate chromosomes during mitosis. In the process we will explore the use of Huxley-type models (population models) of protein binding and unbinding to study load-velocity curves of several different motor-like proteins.
Christine Heitsch : The Combinatorics of RNA Branching
- Mathematical Biology ( 304 Views )Understanding the folding of RNA sequences into three-dimensional structures is one of the fundamental challenges in molecular biology. For example, the branching of an RNA secondary structure is an important molecular characteristic yet difficult to predict correctly, especially for sequences on the scale of viral genomes. However, results from enumerative, probabilistic, analytic, and geometric combinatorics yield insights into RNA structure formation, and suggest new directions in viral capsid assembly.
Shweta Bansal : Got flu? Using small and big data to understand influenza transmission, surveillance and control
- Mathematical Biology ( 301 Views )Traditional infectious disease epidemiology is built on the foundation of high quality and high accuracy data on disease and behavior. While these data are usually characterized by smallsize, they benefit from designed sampling schemes that make it possible to make population-level inferences. On the other hand, digital infectious disease epidemiology uses existing digital traces, re-purposing them to identify patterns in health-related processes. In this talk, I will discuss our work using data from small epidemiological studies as well as administrative “big data” to understand influenza transmission dynamics and inform disease surveillance and control.
Sharon Lubkin : Notochord eccentricity and its relation to cell packing
- Mathematical Biology ( 252 Views )The notochord, the defining feature of chordates, is a pressurized tube which actuates elongation of the chordate embryo. The zebrafish notochord consists of large vacuolated cells surrounded by a thin sheath. We characterized the patterns of the cells’ packing, and their relationship to the known regular patterns from the study of foams, and irregular patterns in a gel bead system. Disruption of the wild type packing pattern leads to developmental defects. We characterize the bifurcations between the relevant regular patterns in terms of nondimensional geometrical and mechanical ratios, and suggest an important developmental role for the eccentric "staircase" pattern.
Rachel Howard : Monitoring the systemic immune response to cancer therapy
- Mathematical Biology ( 246 Views )Complex interactions occur between tumor and host immune system during cancer development and treatment, and a weak systemic immune response can be prognostic of poor patient outcomes. We strive to not only better understand the dynamic behavior of circulating immune cell populations before and during cancer therapy, but also to monitor these dynamic changes to facilitate real-time prediction of patient outcomes and potentially therapy adaptation. I will provide examples of both theoretical (mathematical) and data-driven (epidemiological) approaches to incorporating established systemic immune markers into clinical decision-making. First, coupling models of local tumor-immune dynamics and systemic T cell trafficking allows us to simulate the evolution of tumor and immune cell populations in anatomically distant sites following local therapy, in turn identifying the optimal treatment target for maximum reduction of global tumor burden. Second, improved understanding of how circulating immune markers vary both within and between individual patients can allow more accurate risk stratification at diagnosis, and personalized prediction of patient response to therapy. The importance of multi-disciplinary collaborations in making predictive and prognostic models clinically relevant will be discussed.
Andrew Brouwer : Harnessing environmental surveillance: mathematical modeling in the fight against polio
- Mathematical Biology ( 213 Views )Israel experienced an outbreak of wild poliovirus type 1 (WPV1) in 2013-14, detected through environmental surveillance of the sewage system. No cases of acute flaccid paralysis were reported, and the epidemic subsided after a bivalent oral polio vaccination (bOPV) campaign. As we approach global eradication, polio will increasingly be detected only through environmental surveillance. However, we have lacked the theory to translate environmental surveillance into public health metrics; it is a priori unclear how much environmental surveillance can even say about population-level disease dynamics. We developed a framework to convert quantitative polymerase chain reaction (qPCR) cycle threshold data into scaled WPV1 and OPV1 concentrations for inference within a deterministic, compartmental infectious disease transmission model. We used differential algebra and profile likelihood techniques to perform identifiability analysis, that is, to assess how much information exists in the data for the model, and to quantify inference uncertainty. From the environmental surveillance data, we estimated the epidemic curve and transmission dynamics, determining that the outbreak likely happened much faster than previously thought. Our mathematical modeling approach brings public health relevance to environmental data that, if systematically collected, can guide eradication efforts.
Suncica Canic : Fluid-composite structure interaction and blood flow
- Mathematical Biology ( 210 Views )Fluid-structure interaction problems with composite structures arise in many applications. One example is the interaction between blood flow and arterial walls. Arterial walls are composed of several layers, each with different mechanical characteristics and thickness. No mathematical results exist so far that analyze existence of solutions to nonlinear, fluid-structure interaction problems in which the structure is composed of several layers. In this talk we will summarize the main difficulties in studying this class of problems, and present a computational scheme based on which a proof of the existence of a weak solution was obtained. Our results reveal a new physical regularizing mechanism in FSI problems: inertia of the thin fluid-structure interface with mass regularizes evolution of FSI solutions. Implications of our theoretical results on modeling the human cardiovascular system will be discussed. This is a joint work with Boris Muha (University of Zagreb, Croatia), Martina Bukac (U of Notre Dame, US) and Roland Glowinski (UH). Numerical results with vascular stents were obtained with S. Deparis and D. Forti (EPFL, Switzerland), and with A. Quaini (UH). Collaboration with medical doctors Dr. S. Little (Methodist Hospital Houston) and Dr. Z. Krajcer (Texas Heart Institute) is also acknowledged.
Stanca Ciupe : Models of antibody responses in HIV
- Mathematical Biology ( 174 Views )One of the first immunologic responses against HIV infection is the presence of neutralizing antibodies that seem able to inactivate several HIV strains. Moreover, in vitro studies have shown the existence of monoclonal antibodies that exhibit broad crossclade neutralizing potential. Yet their number is low and slow to develop in vivo. In this paper, we investigate the potential benefits of inducing poly-specific neutralizing antibodies in vivo throughout immunization. We develop a mathematical model that considers the activation of families of B lymphocytes producing poly-specific and strain-specific antibodies and use it to demonstrate that, even if such families are successful in producing neutralizing antibodies, competition between them may limit the poly-specific response allowing the virus to escape. We modify this model to account for viral evolution under the pressure of antibody responses in natural HIV infection as well as the need to neutralize more than one viral spike. The model can reproduce viral escape under certain conditions of B lymphocyte competition. Using these models we provide explanations for the observed antibody failure in controlling natural infection and predict quantitative measures that need to be satisfied for long-term control of HIV infection.
Darryl Shibata : Reconstructing Human Tumor Ancestries from their Genomes: Making Human Tissues Talk
- Mathematical Biology ( 163 Views )It is well-known that genomes encode ancestry through replication errors - on average the greater the numbers of differences between two genomes, the greater the time since they shared a common ancestor ("molecular clock hypothesis"). This approach is commonly used to infer ancestries of species and populations, and these same tools can be applied to somatic cell evolution, in particular to better infer ancestries of normal and neoplastic tissues. For example, by sampling from opposite sides of the same human colorectal tumor, one can coalesce back to the earliest tumor cells. Such studies reveal that many human colorectal tumors are simple single "Big Bang" expansions, with evidence of neutral evolution during growth. It may be possible to understand in detail what is impossible to directly observe - the first few divisions of human tumors.
Aziz Yakubu : Mathematical Models of Malaria with Applications to Mali and USA
- Mathematical Biology ( 148 Views )In this talk, we will introduce a deterministic malaria model for determining the drug administration protocol that leads to the smallest first malaria episodes during the wet season. To explore the effects of administering the malaria drug on different days during wet season while minimizing the potential harmful effects of drug overdose, we will define 40 drug administration protocols. Our results fit well with the clinical studies of Coulibaly et al. at a site in Mali. In addition, we will provide protocols that lead to small number of first malaria episodes during the wet season than the protocol of Coulibaly et al. In the second part of the talk, we will use our malaria model to "capture" the 2013 Centers of Disease Control and Prevention (CDC) reported data on the 2011 number of imported malaria cases in the US. Furthermore; we will use our "fitted" malaria models for the top 20 countries of malaria acquisition by US residents to study the impact of protecting US residents from malaria infection when they travel to malaria endemic areas, the impact of protecting residents of malaria endemic regions from mosquito bites and the impact of killing mosquitoes in those endemic areas on the 2013 CDC malaria surveillance data.
Jim Nolen : Sticky limit theorems for statistics in singular spaces.
- Mathematical Biology ( 147 Views )This talk is about extending classical limit theorems of probability (law of large numbers, central limit theorem) to a non-Euclidean setting. I'll talk about new and interesting phenomena observed when sampling independent points from certain singular geometric spaces. The main result is a limit theorem -- the "sticky central limit theorem" -- which applies to the mean or barycenter of a family of independent samples as the number of samples grows. The theorem shows that the geometry of the underlying space may have an interesting effect on the asymptotic fluctuations of the sample means, in a way that does not occur with independent samples in Euclidean space. One motivation for thinking about statistics in singular geometric spaces comes from evolutionary biology; one can consider phylogenetic trees as points in a metric space of the sort discussed in this talk. Apart from this basic motivation, however, the talk will have little biological content and will be mainly about probability.
Rick Durrett : Branching Process Models of Cancer
- Mathematical Biology ( 145 Views )It is common to use a multitype branching process to model the accumulation of mutations that leads to cancer progression, metastasis, and resistance to treatment. In this talk I will describe results about the time until the first type k (cell with k mutations) and the growth of the type k population obtained in joint work with Stephen Moseley, and their use in evaluating possible screening strategies for ovarian cancer, work in progress with Duke undergraduate Kaveh Danesh. The point process representation of the limit, which is a one-sided stable law, together with results from 10-60 years ago leads to remarkable explicit formulas for Simpson's index and the size of the largest clone. These results are important in understanding tumor diversity which can present serious obstacles to treatment. The last topic is joint work with Jasmine Foo, Kevin Leder, John Mayberry, and Franziska Michor
Steven Baer : Multiscale Modeling of Neural Subcircuits and Feedback Mechanisms in the Outer Plexiform Layer of the Retina
- Mathematical Biology ( 143 Views )Visual processing begins in the outer plexiform layer of the retina, where
bipolar, horizontal, and photoreceptor cells interact. In vertebrates, the
onset of dim backgrounds can enhance small spot flicker responses of
retinal horizontal cells. This flicker response is called background-
induced flicker enhancement. The underlying mechanism for the feedback
is unclear but competing hypotheses have been proposed. One is the GABA
hypothesis, which states that the inhibitory neurotransmitter GABA,
released from horizontal cells, mediates the feedback by blocking calcium
channels. Another is the ephaptic hypothesis, which contends that calcium
entry is regulated by changes in the electrical potential within the
intersynaptic space between cones and horizontal cells. In this study, a
continuum spine model of cone-horizontal cell synaptic circuitry is
formulated. The model captures two spatial scales - the scale of an
individual synapse and the scale of the receptive field involving hundreds
to thousands of synapses. We show that the ephaptic mechanism produces
reasonable qualitative agreement with the temporal dynamics exhibited by
flicker enhancement experiments. We find that although GABA produces
enhancement, this mechanism alone is insufficient to reproduce the
experimental results. We view this multiscale continuum approach as a
first step in formulating a multi-layer mathematical model of retinal
circuitry, which would include the other brain nuclei within the retina:
the inner plexiform layer where bipolar, amacrine, interplexiform, and
ganglion cells interact.
Rodica Curtu : Mixed-Mode Activity Patterns in Neuronal Networks with Lateral Inhibition
- Mathematical Biology ( 141 Views )Stimulus tuning in a reduced model for neural competition leads to
Cecilia Clementi : A multiscale approach to characterize macromolecular dynamics and functions
- Mathematical Biology ( 140 Views )A multiscale approach to characterize macromolecular dynamics and functions The understanding of emerging collective behaviors in biomolecular complexes represents a major challenge in modern biophysics. As a first step toward the study of such processes we have applied multi-resolution nonlinear dimensionality reduction and diffusion analysis to obtain reliable low-dimensional representations and models for the dynamics of apparently high-dimensional complex systems such as proteins in a biological environment. The results clearly show that the proposed methods can efficiently find low dimensional representations of a complex process such as protein folding.
Jill Galagher : Targeting the phenotype: Treatment strategies for heterogeneous cancer
- Mathematical Biology ( 133 Views )Targeted cancer drugs attack pathway specific phenotypes and can lead to very positive outcomes when a particular phenotype dominates the population of a specific tumor. However, these drugs often fail because not all cells express the targeted phenotype to the same degree. This leads to a heterogeneous response to treatment, and ultimate recurrence of the cancer as sensitive cells die off and resistant cells take over. We explore how treatment strategies informed by a tumors phenotypic mix, can help slow the emergence of resistance and stave off tumor recurrence. We use an off-lattice agent-based model that incorporates inheritance of two phenotypes proliferation rate and migration speed and is modulated by a space limiting selection force. We find how and when distinct distributions of phenotypes require different treatment strategies.
Ezra Miller : Applying persistent homology to brain artery and vein imaging
- Mathematical Biology ( 125 Views )Persistent homology measures geometric structures using topological invariants. When the structures are magnetic resonance images of branching arteries, for example, persistent homology records the connectedness of an increasing subset of the vessels. Although the theory of persistent homology is relatively well developed, and many aspects of its behavior are understood in synthetic examples, only recently have applications to genuine experimental data begun. This talk explains what we have learned about the geometry of blood vessels in aging human brains, as well as lessons this exploration has taught us about applications of persistent homology in general. These lessons inform further potential applications of persistent homology in statistical problems from biological and medical imaging. The main results are joint with Paul Bendich, Steve Marron, Aaron Pieloch, and Sean Skwerer (Math junior faculty, Stat faculty, Math undergrad, and Operations Research grad student). The talk will be accessible to advanced mathematics and statistics undergraduates, medical and biological researchers, statistics and mathematics faculty, and everybody in between.
Nicolas Buchler : Coupling of redox rhythms to the plant circadian clock and the yeast cell division cycle .
- Mathematical Biology ( 123 Views )Biological oscillators such as the cell cycle, circadian clocks, and metabolic rhythms are ubiquitous across the domains of life. These biochemical oscillators co-exist in the same cells, often sharing and competing for resources. Are there mechanisms and regulatory principles that ensure harmony between these oscillators? Recent studies have shown that in addition to the transcriptional circadian clock, many organisms (including Arabidopsis) have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. In the first half of my talk, I will describe our work (in collaboration with the Dong lab at Duke) on the coupling of redox rhythms and the plant circadian clock. In the second half of my talk, I will discuss our work on the coupling of yeast metabolic cycle and the cell division cycle.
Tom Kepler : Microevolution in the Immune System: A Computational Systems Approach
- Mathematical Biology ( 122 Views )Vaccines protect their recipients by inducing long-term structural changes in populations of immune cells. Part of that restructuring is exactly analogous to Darwinian Selection. New antibody molecules are created by somatic mutation of existing antibody genes. Subsequently, the immune cell populations that possess these mutated receptors overtake the "wild-type" immune cells due to the selective advantage they have acquired. Thus the immune system is vastly better prepared to recognize and eliminate the eliciting pathogen the next time around.
New sequencing and biosynthesis technologies, together with mathematical and computational tools, now allow us to investigate this fascinating and important phenomenon more deeply than ever before. I will illustrate this development with examples from the immune response to HIV infection.
David Anderson : Stochastic models of biochemical reaction systems: network structure and qualitative dynamics
- Mathematical Biology ( 113 Views )Biochemical reaction networks can be represented as graphs, with chemical complexes serving as vertices and reaction channels serving as directed edges. To each such network there is an associated stochastic process that models the behavior of the underlying system of interest. In this talk I will present results that relate the structure of the reaction network to the possible dynamics of the model. I will pay particular attention to how the results pertaining to the stochastic models compare and contrast with similar results pertaining to deterministic models.
Sayan Mukherjee : Modeling a Male-Male Sex Network in South India for Spread of Disease and Behavior
- Mathematical Biology ( 109 Views )A preliminary examination of a very rich data set consisting of a detailed survey of individuals in male-male sex networks in South India. The motivation for the study is to understand the spread of HIV in male-male sex networks in South India. The data contains survey information from participants, as well as their cell phone contacts and incomplete information on the contacts by participants. We provide predictive models of attributes of contacts given participant attributes, as well as predictive models of the attributes, such as sexual position. We study how model parameters vary as a function of connectedness of individuals and how modeling network interactions has an effect on the model.
Suzanne Lenhart : Optimal Harvesting in Fishery Models
- Mathematical Biology ( 106 Views )We discuss two types of partial differential equation models of fishery harvesting problems. We consider steady state spatial models and diffusive spatial-temporal models. We characterize the distribution of harvest effort which maximizes the harvest yield, and in the steady state case, also minimizes the cost of the effort. We show numerical results to illustrate various cases. The results inform ongoing debate about the use of reserves (regions where fishing is not allowed), and are increasingly relevant as technology enables enforcement of spatially structured harvest constraints.
Sorin Mitran : Information Theoretic Projection of Cytoskeleton Dynamics onto Surrogate Cellular Motility Models
- Mathematical Biology ( 106 Views )Cellular motility arises from the interaction of numerous components: actin filaments, ligands, adhesion complexes to name a few. Each individual component exhibits stochastic behavior, yet overall cooperative behavior is observed, and leads to motility. Linking overall cellular motion to the stochastic behavior of its components is a remarkable mathematical challenge. This talk introduces a method to cyclically extract surrogate motility models from detailed stochastic simulation of the components. The starting point is a sampling of the detailed cytoskeleton dynamics over a short time interval. This detailed information is repeatedly projected onto a lower dimensional statistical manifold to obtain a coarse-grained model of the cytoskeleton, from which a surrogate cell model is obtained. The projection operation corresponds to transport along the geodesics of embedded statistical manifolds. The surrogate model is advanced over a larger time interval and then used to recreate the detailed microscopic cytoskeleton state needed to start the next cycle. The procedure is applied to study the behavior of Listeria monocytogenes bacterium and inert models of the motility behavior of this bacterium
Sean Lawley : Stochastics in medicine: Delaying menopause and missing drug doses
- Mathematical Biology ( 104 Views )Stochastic modeling and analysis can help answer pressing medical questions. In this talk, I will attempt to justify this claim by describing recent work on two problems in medicine. The first problem concerns ovarian tissue cryopreservation, which is a proven tool to preserve ovarian follicles prior to gonadotoxic treatments. Can this procedure be applied to healthy women to delay or eliminate menopause? How can it be optimized? The second problem concerns medication nonadherence. What should you do if you miss a dose of medication? How can physicians design dosing regimens that are robust to missed/late doses? I will describe (a) how stochastics theory offers insights into these questions and (b) the mathematical questions that emerge from this investigation. The first problem is based on joint work with Joshua Johnson (University of Colorado School of Medicine), John Emerson (Yale University), and Kutluk Oktay (Yale School of Medicine).
Sorin Mitran : Cytoskeleton multiscale model
- Mathematical Biology ( 99 Views )One of the challenges in biology is relating biochemical reactions that occur at the protein nanoparticle size of 1-100 nm to large scale effects on the cell or tissue scale of 0.01-10 mm. The cytoskeleton is a remarkable example with actin polymerization/depolymerization leading to locomotion, metastasis or apoptosis. This talk presents a recently developed multiscale model that captures large-scale effects produced by changes in biochemical reactions. The model is a computational algorithm that determines effective continuum properties of a homogenized cytoskeleton model by concurrent microscopic simulation. Concepts from information theory and optimal transport are applied to link disparate scales in a computationally efficient manner. One of the interesting aspects of this approach is the combination of standard computational modeling techniques (finite volume, numerical stochastic ODEs) with statistical concepts and learning theory.
Punit Gandhi : Conceptual modeling of dryland vegetation patterns across timescales
- Mathematical Biology ( 91 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.
Paula Vasquez : Coupling macro-micro simulations in biological fluids
- Mathematical Biology ( 0 Views )Some of the most remarkable properties and functions served by complex fluids originate from the interplay between external fields and microstructural dynamics. From a computational point of view this generates a set of challenges related to the need of coupling dynamics at different length and times scales, sometimes spanning several orders of magnitude. Micro-macro simulations have gained a lot of recognition within the field because these methods allow capturing full dynamics at the macroscale without losing resolution at the microscale. In this talk, we will review our efforts to couple existing macroscopic solvers for the Navier-Stokes equations with microstructural dynamics described by Langevin-type equations. In particular, we will discuss dumbbells models -under viscometric and capillary thinning flows fields- and parallel computing using GPUs.