Perspectives from computational algebra and numerical optimization are brought to bear on a scientific application and a data science application. In the first part of the talk, I will discuss cryo-electron microscopy (cryo-EM), an imaging technique to determine the 3-D shape of macromolecules from many noisy 2-D projections, recognized by the 2017 Chemistry Nobel Prize. Mathematically, cryo-EM presents a particularly rich inverse problem, with unknown orientations, extreme noise, big data and conformational heterogeneity. In particular, this motivates a general framework for statistical estimation under compact group actions, connecting information theory and group invariant theory. In the second part of the talk, I will discuss tensor rank decomposition, a higher-order variant of PCA broadly applicable in data science. A fast algorithm is introduced and analyzed, combining ideas of Sylvester and the power method.

Computational protein design is a transformative field with exciting prospects for advancing both basic science and translational medical research. New algorithms blend discrete and continuous mathematics to address the challenges of creating designer proteins. I will discuss recent progress in this area and some interesting open problems. I will motivate this talk by discussing how, by using continuous geometric representations within a discrete optimization framework, broadly-neutralizing anti-HIV-1 antibodies were computationally designed that are now being tested in humans - the designed antibodies are currently in eight clinical trials (See https://clinicaltrials.gov/ct2/results?cond=&term=VRC07&cntry=&state=&city=&dist= ), one of which is Phase 2a (NCT03721510). These continuous representations model the flexibility and dynamics of biological macromolecules, which are an important structural determinant of function. However, reconstruction of biomolecular dynamics from experimental observables requires the determination of a conformational probability distribution. These distributions are not fully constrained by the limited information from experiments, making the problem ill-posed in the sense of Hadamard. The ill-posed nature of the problem comes from the fact that it has no unique solution. Multiple or even an infinite number of solutions may exist. To avoid the ill-posed nature, the problem must be regularized by making (hopefully reasonable) assumptions. I will present new ways to both represent and visualize correlated inter-domain protein motions (See Figure). We use Bingham distributions, based on a quaternion fit to circular moments of a physics-based quadratic form. To find the optimal solution for the distribution, we designed an efficient, provable branch-and-bound algorithm that exploits the structure of analytical solutions to the trigonometric moment problem. Hence, continuous conformational PDFs can be determined directly from NMR measurements. The representation works especially well for multi-domain systems with broad conformational distributions. Ultimately, this method has parallels to other branches of applied mathematics that balance discrete and continuous representations, including physical geometric algorithms, robotics, computer vision, and robust optimization. I will advocate for using continuous distributions for protein modeling, and describe future work and open problems.

The classical Hardy-Littlewood maximal operators (averaging over families of Euclidean balls and cubes) are known to satisfy L^p bounds that are independent of dimension. This talk will extend these results to spherical maximal functions acting on Cartesian products of cyclic groups equipped with the Hamming metric.

Nonlocal models are experiencing a firm upswing recently as more realistic alternatives to the conventional local models for studying various phenomena from physics and biology to materials and social sciences. In this talk, I will describe our recent effort in taming the computational challenges for nonlocal models. I will first highlight a family of numerical schemes -- the asymptotically compatible schemes -- for nonlocal models that are robust with the modeling parameter approaching an asymptotic limit. Second, fast algorithms will be presented to reduce the high computational cost from the numerical implementation of the nonlocal operators. Although new nonlocal models have been gaining popularity in various applications, they often appear as phenomenological models, such as the peridynamics model in fracture mechanics. Here we will try to provide better perspectives of the origin of nonlocality from multiscale modeling and homogenization, which in turn may help the development of more effective numerical methods for homogenization.

We first discuss a general method to derive macroscopic laws from certain microscopic interactions that can be applied to a large class of particle systems. In particular we consider a broad class of systems that are linear in a special algebra, so-called tropical algebra. Some natural connections among the scaling limits of these random systems, the solutions to specific partial differential equations (Hamilton-Jacobi type) and combinatorial optimization problems have been noticed. If time allows, we further discuss a useful application of the variational formula (microscopic version of Hopf-Lax formula) to a well-known interacting particle system, totally asymmetric simple exclusion process.

The optimal transport (Monge-Kantorovich) problem is a variational problem involving transportation of mass subject to minimizing some kind of energy, and it arises in connection with many parts of math, both pure and applied. In this talk, I will discuss a numerical algorithm to approximate solutions in the semi-discrete case. We propose a damped Newton algorithm which exploits the structure of the associated dual problem, and using geometric implications of the regularity theory of Monge-Amp{\`e}re equations, we are able to rigorously prove global linear convergence and local superlinear convergence of the algorithm. This talk is based on joint work with Quentin M{\’e}rigot and Boris Thibert.

We will discuss two issues in the context of applying deep learning methods to multi-scale molecular modelling: 1) how to construct symmetry-preserving neural network models for scalar and tensorial quantities; 2) how to efficiently explore the relevant configuration space and generate a minimal set of training data. We show that by properly addressing these two issues, one can systematically develop deep learning-based models for electronic properties and interatomic and coarse-grained potentials, which greatly boost the ability of ab-initio molecular dynamics; one can also develop enhanced sampling techniques that are capable of using tens or even hundreds of collective variables to drive phase transition and accelerate structure search

Given two probability measures and a transportation cost, the optimal transport problem asks to find the most cost efficient way to transport one measure to the other. Since its introduction in 1781 by Gaspard Monge, the optimal transport problem has found applications in logistics, economics, physics, PDEs, and more recently data science. However, despite sustained attention from the numerics community, solving optimal transport problems has been a notoriously difficult task. In this talk I will introduce the back-and-forth method, a new algorithm to efficiently solve the optimal transportation problem for a general class of strictly convex transportation costs. Given two probability measures supported on a discrete grid with n points, the method computes the optimal map in O(n log(n)) operations using O(n) storage space. As a result, the method can compute highly accurate solutions to optimal transportation problems on spatial grids as large as 4096 x 4096 and 384 x 384 x 384 in a matter of minutes. If time permits, I will demonstrate an extension of the algorithm to the simulation of a class of gradient flows. This talk is joint work with Flavien Leger.

An effort at UNC is involved in understanding key mechanisms in the lung related to defense against pathogens. In diseases ranging from Cystic Fibrosis to asthma, these mechanisms are highly compromised, requiring therapeutic strategies that one would like to be able to quantify or even predict in some way. The Virtual Lung Project has focused on one principal component of lung defense: "the mucus escalator" as it is called in physiology texts. My goal in this lecture, with apologies to Tina Turner, is to give a longwinded answer to "what's math got to do with it?", and at the same time to convey how this collaboration is influencing the applied mathematics experience at UNC.

A pressure difference across a liquid layer will accelerate it. For incompressible and inviscid motion, it is possible to describe the motion of the surfaces through boundary integral techniques. In particular, dipole distributions can be used together with an external flow that specifies the acceleration. The classical Rayleigh-Taylor instability and the creation of bubbles at an orifice are two important applications. A new method for the numerical approximation of the boundary integrals removes the difficulties associate with surfaces in close proximity.

Boundary value and interface problems for the Laplace equation are often solved by boundary integral methods due to the reduction of dimensionality and its flexibility in domain geometry. However, there are two well-known computational issues with the boundary integral method: (a) evaluation of boundary integrals at points close to domain boundaries usually has low order accuracy; (b) the method typically yields dense coefficient matrices in the resulting discrete systems, which makes the matrix vector multiplication very expensive when the size of the system is very large. In this talk, I will describe a fast accurate boundary integral method for the Laplace boundary value and interface problems. The algorithm uses the high order accurate method proposed by (Beale and Lai 2001) for evaluation of the boundary integrals and applies the fast multipole method for the dense matrix vector multiplication. Numerical results demonstrating the efficiency and accuracy of the method will be presented.

Blood vessel systems and leaf venations are typical biological transport networks. The energy consumption for such a system to perform its biological functions is determined by the network structure. In the first part of this talk, I will discuss the optimized structure of vessel networks, and show how the blood vessel system adapts itself to an optimized structure. Mathematical models are used to predict pruning vessels in the experiments of zebra fish. In the second part, I will discuss our recent modeling work on the initiation process of transport networks. Simulation results are used to illustrate how a tree-like structure is obtained from a continuum adaptation equation system, and how loops can exist in our model. Possible further application of this model will also be discussed.

Chemotaxis plays a crucial role in a variety of processes in biology and ecology. One of the most studied PDE models of chemotaxis is given by Keller-Segel equation, which describes a population density of bacteria or mold which attract chemically to substance they secrete. However, solution of Keller-Segel equation can exhibit dramatic collapsing behavior. In other words, there exist initial data leading to finite time blow up. In this talk, we will discuss the possible effects resulting from interaction of chemotactic and fluid transport processes, namely we will consider the Keller-Segel equation with additional advection term modeling ambient fluid flow. We will prove that the presence of fluid can prevent the singularity formation. We will discuss two classes of flows that have the explosion arresting property. Both classes are known as very efficient mixers.

The study of various questions about networks have increased dramatically in recent years across a number of areas of application, including communications, sociology, and phylogenetic biology. Important questions about communities and groupings in networks have led to a number of competing techniques for identifying communities, structures and hierarchies. We discuss results about the networks of (1) NCAA Division I-A college football matchups and (2) committee assignments in the U.S. House of Representatives. In college football, the underlying structure of the network strongly influences the computer rankings that contribute to the Bowl Championship Series standings. In Congress, the changes of the hierarchical structure from one Congress to the next can be used to investigate major political events, such as the "Republican Revolution" of 1994 and the introduction of the Select Committee on Homeland Security following September 11th. While many structural elements in each case are seemingly robust, we include attention to variations across identification algorithms as we investigate the roles of such structures.

An efficient method for simulating the propagation of a localized solution of the Schroedinger equation near the semiclassical limit is presented. The method is based on a time dependent transformation closely related to Gaussian wave packets and yields a Schroedinger type equation that is very ammenable to numerical solution in the semi-classical limit. The wavefunction can be reconstructed from the transformed wavefunction whereas expectation values can easily be evaluated directly from the transformed wavefunction. The number of grid points needed per degree of freedom is small enough that computations in dimensions of up to 4 or 5 are feasible without the use of any basis thinning procedures. This is joint work with Giovanni Russo.

Arnold diffusion is the phenomenon of loss of stability of a completely integrable Hamiltonian system: an arbitrarily small perturbation can cause action to change along some orbit by a finite amount. Arnold produced the first example of diffusion and gave an outline of the proof. After a brief overview of related results I will describe the simplest example of Arnold diffusion which we found recently with Vadim Kaloshin. We consider geodesics on the 3-torus, or equivalently rays in a periodic optical medium in $ {\mathbb R} ^3 $ (or equivalently a point mass in a periodic potential in $ {\mathbb R} ^3 $.) Arnold diffusion has a transparent intuitive explanation and a simple proof. Resonances and the so-called ``whiskered tori" acquire a clear geometrical interpretation as well. I will conclude with a sketch of a different but related manifestation of Arnold diffusion as acceleration of a particle by a pulsating potential. This is joint work with Vadim Kaloshin.

We have witnessed a lot of exciting development of data science in recent years. From the perspective of optimization, many modern data-science problems involve some basic ``non’’-properties that lack systematic treatment by the current approaches for the sake of the computation convenience. These non-properties include the coupling of the non-convexity, non-differentiability and non-determinism. In this talk, we present rigorous computational methods for solving two typical non-problems: the piecewise linear regression and the feed-forward deep neural network. The algorithmic framework is an integration of the first order non-convex majorization-minimization method and the second order non-smooth Newton methods. Numerical experiments demonstrate the effectiveness of our proposed approach. Contrary to existing methods for solving non-problems which provide at best very weak guarantees on the computed solutions obtained in practical implementation, our rigorous mathematical treatment aims to understand properties of these computed solutions with reference to both the empirical and the population risk minimizations. This is based on joint work with Jong-Shi Pang, Bodhisattva Sen and Ziyu He.

The Fermi-Pasta-Ulam (FPU) model of coupled anharmonic oscillators has long been of interest in nonlinear science. It is only recently (Friesecke and Wattis 1994, Frieseck and Pego 1999-2003, and Mizumachi (submitted)) that the existence and stability of solitary waves in FPU has been completely understood. In light of the fact that the Korteweg-deVries (KdV) equation may recovered as a long wave limit of FPU and that the theory of soliton interaction is both beautiful and completely understood in KdV, it is of interest to describe the interaction of two colliding solitary waves in the FPU model. We show that the FPU model contains an open set of solutions which remain close to the linear sum of two long wave low amplitude solitions as time goes to either positive or negative infinity.

The Explicit Jump Immersed Interface Method (EJIIM) is a finite difference method for elliptic partial differential equations that, like all Immersed Interface Methods, works on a regular grid in spite of non-grid aligned discontinuities in equation parameters and solution. The specific idea is to introduce jumps in function and its derivatives explicitely as additional variables. We present a finite difference based EJIIM for the stationary Stokes flow in saddle point formulation. Challenges related to staggered grid, fast Stokes solver and non-simply connected domains will be discussed.

A wide range of viral infections, such as HIV or influenza, can now be treated using antiviral drugs. Since viruses can evolve rapidly, the emergence and spread of drug resistant virus strains is a major concern. We shall describe within and between host models that can help indicate settings in which resistance is more or less likely to be problematic. In particular, we shall discuss the potential for the emergence of resistance in the context of human rhinovirus infection, an acute infection that is responsible for a large fraction of 'common cold' cases.

We begin with an introduction to time-dependent quantum mechanics and the role of Planck's constant. We then describe some mathematical results about solutions to the Schr\"odinger equation for small values of the Planck constant. Finally, we discuss two new numerical techniques for semiclassical quantum dynamics, including one that is a work in progress.

In computational physics, molecular dynamics refers to the computer simulation of a material at the atomic level. I will consider classical deterministic molecular dynamics in which large Hamiltonian systems of ordinary differential equations are used, though many of the same issues arise with other models. Given its scientific importance there is very little rigorous justification of molecular dynamics. From the viewpoint of numerical analysis it is surprising that it works at all. The problem is that individual trajectories computed by molecular dynamics are accurate for only small time intervals, whereas researchers trust the results over very long time intervals. It has been conjectured that molecular dynamics trajectories are accurate over long time intervals in some weak statistical sense. Another conjecture is that numerical trajectories satisfy the shadowing property: that they are close over long time intervals to exact trajectories with different initial conditions. I will explain how these two views are actually equivalent to each other, after we suitably modify the concept of shadowing.

A new numerical method being developed with Charles Peskin is described which simulates interacting fluid, membrane, and particle systems in which thermal fluctuations play an important role. This method builds on the "Immersed Boundary Method" of Peskin and McQueen, which simplifies the coupling between the fluid and the immersed particles and membranes in such a way as to avoid complex boundary problems. Thermal fluctuations are introduced in the fluid through the theory of statistical hydrodynamics. We discuss some approximate analytical calculations which indicate that the immersed particles should exhibit some physically correct properties of Brownian motion. Our intended use of this numerical method is to simulate microphysiological processes; one advantage this method would have over Langevin particle dynamics approaches is its explicit tracking of the role of the fluid dynamics.

The simplest example of a boundary value problem is the Dirichlet Poisson problem: we seek to recover a function, defined on a smooth domain, its values at the boundary of the domain and the divergence of its gradient for all points inside the domain. This problem has been studied for more than 200 years, and has many applications in science and engineering. Analytic solutions are available only for a limited number of cases. Therefore one has to use a numerical method. The basic goals in designing a numerical method is guaranteed quality of the solution, in reasonable time, in a black-box fashion. Surprisingly, a robust, black-box, algorithmically scalable method for the Poisson problem does not exist. The main difficulties are related to robust mesh generation in complex geometries in three dimensions. I will review different approaches in solving the Poisson problem and present a new method based on classical Fredholm integral equation formulation. The main components of the new method are a kernel-independent fast summation method, manifold surface representations, and superalgebraically accurate quadrature methods. The method directly extends to problems with non-oscillatory known Green's functions. In addition to the Poisson problem I will present results for the Navier, modified Poisson, and Stokes operators.

Whenever we wish to determine the characteristics of an object based on data of how it scatters incoming radiation we must solve an inverse scattering problem. This is a frequent situation in many fields, such as geophysical imaging or biomedical imaging. To reconstruct objects from the measured data, we can design optimization problems in which the boundary value problems governing the incident radiation act as constraints. Then we implement descent techniques to approach a global minimum. However, the process may stagnate without converging, either due to lack of convexity or to small gradients. We propose a method to overcome this difficulty combining topological derivative based optimization to generate first approximations with iteratively regularized Gauss-Newton techniques to ensure convergence. Numerical simulations illustrate fast reconstruction of objects formed by multiple non convex components in extreme situations such as holographic microscopy set-ups, in which the only data available are intensity measurements for one incident light beam on a limited screen.

Coarsening is the phenomenon where many objects (water drops, molecular islands, particles in a freezing liquid) becoming smaller in number but larger in size in an orderly way. This talk will examine modeling one such system, nanoscopic liquid drops, through three models: a PDE for the fluid, a coarsening dynamical system for the drops, and an LSW-type ensemble model for the distribution of drops. We will find self-similar solutions for the drop population valid for intermediate times and discuss transient effects that can delay the self-similar scaling.

It is well-known that the asymptotic complexity of matrix-matrix product and matrix inversion is given by the rank of a 3-tensor, recently shown to be at most O(n^2.3728639) by Le Gall. This approach is attractive as a rank decomposition of that 3-tensor gives an explicit algorithm that is guaranteed to be fastest possible and its tensor nuclear norm quantifies the optimal numerical stability. There is also an alternative approach due to Cohn and Umans that relies on embedding matrices into group algebras. We will see that the tensor decomposition and group algebra approaches, when combined, allow one to systematically discover fast(est) algorithms. We will determine the exact (as opposed to asymptotic) tensor ranks, and correspondingly the fastest algorithms, for products of Circulant, Toeplitz, Hankel, and other structured matrices. This is joint work with Ke Ye (Chicago).

I will start with the deterministic dynamics generated by a vector field that has several unstable critical points connected by heteroclinic orbits. A perturbation of this system by white noise will be considered. I will study the limit of the resulting stochastic system in distribution (under appropriate time rescaling) as the noise intensity vanishes. It is possible to describe the limiting process in detail, and, in particular, interesting non-Markov effects arise. There are situations where this result provides more precise exit asymptotics than the classical Wentzell-Freidlin theory.

In this talk, we will introduce a dynamic mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV). Using optimal control theory, we will illustrate that optimal dynamic multidrug therapies can produce a drug dosing strategy that exhibits structured treatment interruption, a regimen in which patients are cycled on and off therapy. In addition, sensitivity analysis of the model including both classical sensitivity functions and generalized sensitivity functions will be presented. Finally, we will describe how stochastic estimation can be used to filter and estimate states and parameters from noisy data. In the course of this analysis it will be shown that automatic differentiation can be a powerful tool for this type of study.