Paul Bourgine

Bio: Paul Bourgine is an academic researcher from Lund University. The author has contributed to research in topics: Mesenchymal stem cell & Stromal cell. The author has an hindex of 28, co-authored 99 publications receiving 6376 citations. Previous affiliations of Paul Bourgine include University Hospital of Basel & Université Paris-Saclay.

Distributed Optimization by Ant Colonies

Abstract: Ants colonies exhibit very interesting behaviours: even if a single ant only has simple capabilities, the behaviour of a whole ant colony is highly structured. This is the result of coordinated interactions. But, as communication possibilities among ants are very limited, interactions must be based on very simple flows of information. In this paper we explore the implications that the study of ants behaviour can have on problem solving and optimization. We introduce a distributed problem solving environment and propose its use to search for a solution to the travelling salesman problem.

Topological and causal structure of the yeast transcriptional regulatory network.

Abstract: Interpretation of high-throughput biological data requires a knowledge of the design principles underlying the networks that sustain cellular functions. Of particular importance is the genetic network, a set of genes that interact through directed transcriptional regulation. Genes that exert a regulatory role encode dedicated transcription factors (hereafter referred to as regulating proteins) that can bind to specific DNA control regions of regulated genes to activate or inhibit their transcription. Regulated genes may themselves act in a regulatory manner, in which case they participate in a causal pathway. Looping pathways form feedback circuits. Because a gene can have several connections, circuits and pathways may crosslink and thus represent connected components. We have created a graph of 909 genetically or biochemically established interactions among 491 yeast genes. The number of regulating proteins per regulated gene has a narrow distribution with an exponential decay. The number of regulated genes per regulating protein has a broader distribution with a decay resembling a power law. Assuming in computer-generated graphs that gene connections fulfill these distributions but are otherwise random, the local clustering of connections and the number of short feedback circuits are largely underestimated. This deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.

Cell Lineage Reconstruction of Early Zebrafish Embryos Using Label-Free Nonlinear Microscopy

Abstract: Quantifying cell behaviors in animal early embryogenesis remains a challenging issue requiring in toto imaging and automated image analysis. We designed a framework for imaging and reconstructing unstained whole zebrafish embryos for their first 10 cell division cycles and report measurements along the cell lineage with micrometer spatial resolution and minute temporal accuracy. Point-scanning multiphoton excitation optimized to preferentially probe the innermost regions of the embryo provided intrinsic signals highlighting all mitotic spindles and cell boundaries. Automated image analysis revealed the phenomenology of cell proliferation. Blastomeres continuously drift out of synchrony. After the 32-cell stage, the cell cycle lengthens according to cell radial position, leading to apparent division waves. Progressive amplification of this process is the rule, contrasting with classical descriptions of abrupt changes in the system dynamics.

Engineering of a functional bone organ through endochondral ossification.

Abstract: Embryonic development, lengthening, and repair of most bones proceed by endochondral ossification, namely through formation of a cartilage intermediate. It was previously demonstrated that adult human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) can execute an endochondral program and ectopically generate mature bone. Here we hypothesized that hMSCs pushed through endochondral ossification can engineer a scaled-up ossicle with features of a “bone organ,” including physiologically remodeled bone, mature vasculature, and a fully functional hematopoietic compartment. Engineered hypertrophic cartilage required IL-1β to be efficiently remodeled into bone and bone marrow upon subcutaneous implantation. This model allowed distinguishing, by analogy with bone development and repair, an outer, cortical-like perichondral bone, generated mainly by host cells and laid over a premineralized area, and an inner, trabecular-like, endochondral bone, generated mainly by the human cells and formed over the cartilaginous template. Hypertrophic cartilage remodeling was paralleled by ingrowth of blood vessels, displaying sinusoid-like structures and stabilized by pericytic cells. Marrow cavities of the ossicles contained phenotypically defined hematopoietic stem cells and progenitor cells at similar frequencies as native bones, and marrow from ossicles reconstituted multilineage long-term hematopoiesis in lethally irradiated mice. This study, by invoking a “developmental engineering” paradigm, reports the generation by appropriately instructed hMSC of an ectopic “bone organ” with a size, structure, and functionality comparable to native bones. The work thus provides a model useful for fundamental and translational studies of bone morphogenesis and regeneration, as well as for the controlled manipulation of hematopoietic stem cell niches in physiology and pathology.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The Structure and Function of Complex Networks

Abstract: Inspired by empirical studies of networked systems such as the Internet, social networks, and biological networks, researchers have in recent years developed a variety of techniques and models to help us understand or predict the behavior of these systems. Here we review developments in this field, including such concepts as the small-world effect, degree distributions, clustering, network correlations, random graph models, models of network growth and preferential attachment, and dynamical processes taking place on networks.

Genetic Programming: On the Programming of Computers by Means of Natural Selection

Abstract: Background on genetic algorithms, LISP, and genetic programming hierarchical problem-solving introduction to automatically-defined functions - the two-boxes problem problems that straddle the breakeven point for computational effort Boolean parity functions determining the architecture of the program the lawnmower problem the bumblebee problem the increasing benefits of ADFs as problems are scaled up finding an impulse response function artificial ant on the San Mateo trail obstacle-avoiding robot the minesweeper problem automatic discovery of detectors for letter recognition flushes and four-of-a-kinds in a pinochle deck introduction to biochemistry and molecular biology prediction of transmembrane domains in proteins prediction of omega loops in proteins lookahead version of the transmembrane problem evolutionary selection of the architecture of the program evolution of primitives and sufficiency evolutionary selection of terminals evolution of closure simultaneous evolution of architecture, primitive functions, terminals, sufficiency, and closure the role of representation and the lens effect Appendices: list of special symbols list of special functions list of type fonts default parameters computer implementation annotated bibliography of genetic programming electronic mailing list and public repository

Ant system: optimization by a colony of cooperating agents

Abstract: An analogy with the way ant colonies function has suggested the definition of a new computational paradigm, which we call ant system (AS). We propose it as a viable new approach to stochastic combinatorial optimization. The main characteristics of this model are positive feedback, distributed computation, and the use of a constructive greedy heuristic. Positive feedback accounts for rapid discovery of good solutions, distributed computation avoids premature convergence, and the greedy heuristic helps find acceptable solutions in the early stages of the search process. We apply the proposed methodology to the classical traveling salesman problem (TSP), and report simulation results. We also discuss parameter selection and the early setups of the model, and compare it with tabu search and simulated annealing using TSP. To demonstrate the robustness of the approach, we show how the ant system (AS) can be applied to other optimization problems like the asymmetric traveling salesman, the quadratic assignment and the job-shop scheduling. Finally we discuss the salient characteristics-global data structure revision, distributed communication and probabilistic transitions of the AS.