Computational Model Reveals a Stochastic Mechanism behind Germinal Center Clonal Bursts.
Pelissier, A.; Akrout, Y.; Jahn, K.; Kuipers, J.; Klein, U.; Beerenwinkel, N.; Rodriguez Martinez, M.
Cells 9(6), 1448, 2020
Germinal centers (GCs) are specialized compartments within the secondary lymphoid organs where B cells proliferate, differentiate, and mutate their antibody genes in response to the presence of foreign antigens. Through the GC lifespan, interclonal competition between B cells leads to increased affinity of the B cell receptors for antigens accompanied by a loss of clonal diversity, although the mechanisms underlying clonal dynamics are not completely understood. We present here a multi-scale quantitative model of the GC reaction that integrates an intracellular component, accounting for the genetic events that shape B cell differentiation, and an extracellular stochastic component, which accounts for the random cellular interactions within the GC. In addition, B cell receptors are represented as sequences of nucleotides that mature and diversify through somatic hypermutations. We exploit extensive experimental characterizations of the GC dynamics to parameterize our model, and visualize affinity maturation by means of evolutionary phylogenetic trees. Our explicit modeling of B cell maturation enables us to characterise the evolutionary processes and competition at the heart of the GC dynamics, and explains the emergence of clonal dominance as a result of initially small stochastic advantages in the affinity to antigen. Interestingly, a subset of the GC undergoes massive expansion of higher-affinity B cell variants (clonal bursts), leading to a loss of clonal diversity at a significantly faster rate than in GCs that do not exhibit clonal dominance. Our work contributes towards an in silico vaccine design, and has implications for the better understanding of the mechanisms underlying autoimmune disease and GC-derived lymphomas.
Feature selection as Monte-Carlo Search in Growing Single Rooted Directed Acyclic Graph by Best Leaf Identification
Aurelien Pelissier, Atsuyoshi Nakamura, Koji Tabata
Proceedings of the 2019 SIAM International Conference on Data Mining
Monte Carlo tree search (MCTS) has received considerable interest due to its spectacular success in the difficult problem of computer Go and also proved beneficial in a range of other domains. A major issue that has received little attention in the MCTS literature is the fact that, in most games, different actions can lead to the same state, that may lead to a high degree of redundancy in tree representation and unnecessary additional computational cost. We extend MCTS to single rooted directed acyclic graph (SR-DAG), and consider the Best Arm Identification (BAI) and the Best Leaf Identification (BLI) problem of an expanding SR-DAG of arbitrary depth. We propose algorithms that are (epsilon, delta)-correct in the fixed confidence setting, and prove an asymptotic upper bounds of sample complexity for our BAI algorithm. As a major application for our BLI algorithm, a novel approach for Feature Selection is proposed by representing the feature set space as a SR-DAG and repeatedly evaluating feature subsets until a candidate for the best leaf is returned, a proof of concept is shown on benchmark data sets.
Coupling of a single active nanoparticle to a polymer-based photonic structure
Dam Thuy Trang Nguyen, Thi Huong Au, Quang Cong Tong, Mai Hoang Luong, Aurelien Pelissier, Kevin Montes, Hoang Minh Ngo, Minh Thanh Do, Danh Bich Do, Duc Thien Trinh, Thanh Huong Nguyen, Bruno Palpant, Chia Chen Hsu, Isabelle Ledoux-Rak, Ngoc Diep Lai
Journal of Science: Advanced Materials and Devices 1(1), 18-30, 2016
Abstract 1 2 The engineered coupling between a guest moiety (molecule, nanoparticle) and the host photonic nanostructure may provide a great enhancement of the guest optical response, leading to many attractive applications. In this article, we describe briefly the basic concept and some recent progress considering the coupling of a single nanoparticle into a photonic structure. Different kinds of nanoparticles of great interest including quantum dots and nitrogen-vacancy centers in nanodiamond for single photon source, nonlinear nanoparticles for efficient nonlinear effect and sensors, magnetic nanoparticles for Kerr magneto-optical effect, and plasmonic nanoparticles for ultrafast optical switching and sensors, are briefly reviewed. We focus further on the coupling of plasmonic gold nanoparticles and polymeric photonic structures by optimizing theoretically the photonic structures and developing efficient way to realize desired hybrid structures. The simple and low-cost fabrication technique, the optical enhancement of the fluorescent nanoparticles induced by the photonic structure, as well as the limitations, challenges and appealing prospects are discussed in details.
Deterministic embedding of a single gold nanoparticle into polymeric microstructures by direct laser writing technique
Dam Thuy Trang Nguyen, Aurelien Pelissier, Kevin Montes, Quang Cong Tong, Hoang Minh Ngo, Isabelle Ledoux-Rak, Ngoc Diep Lai
SPIE Photonics Europe9884, 2016
We have precisely positioned and embedded a single gold nanoparticle (Au NP) into a desired polymeric photonic structure (PS) using a simple and low-cost technique called low one-photon absorption direct laser writing (LOPA DLW), with a two-step process: identification and fabrication. First, the position of the Au NP was identified with a precision of 20 nm by using DLW technique with ultralow excitation laser power (W). This power did not induce the polymerization of the photoresist (SU8) due to its low absorption at the excitation wavelength (532 nm). Then, the structure containing the NP was fabricated by using the same DLW system with high excitation power (mW). Different 2D photonic structures have been fabricated, which contain a single Au NP at desired position. In particular, we obtained a microsphere instead of a micropillar at the position of the Au NP. The formation of such microsphere was explained by the thermal effect of the Au NP at the wavelength of 532 nm, which induced thermal polymerization of surrounding photoresist. The effect of the post-exposure bake on the quality of structures was taken into account, revealing a more efficient fabrication way by exploiting the local thermal effect of the laser. 198 We 200 studied further the influence of the NP size on the NP/PS coupling 213 by investigating the fabrication and fluorescence measurement of Au NPs of different sizes: 10, 30, 50, 80, and 100 nm. The photon collection enhancements in each case were 12.9 2.5, 12.6 5.6, 3.9 2.7, 5.9 4.4, and6.6 5.1 times, respectively. The gain in fluorescence could reach up to 36.6 times for 10-nm gold NPs.