École Nationale Supérieure des Mines de Paris

A fast and flexible algorithm for computing watersheds in digital gray-scale images is introduced. A review of watersheds and related motion is first presented, and the major methods to determine watersheds are discussed. The algorithm is based on an immersion process analogy, in which the flooding of the water in the picture is efficiently simulated using of queue of pixel. It is described in detail provided in a pseudo C language. The accuracy of this algorithm is proven to be superior to that of the existing implementations, and it is shown that its adaptation to any kind of digital grid and its generalization to n-dimensional images (and even to graphs) are straightforward. The algorithm is reported to be faster than any other watershed algorithm. Applications of this algorithm with regard to picture segmentation are presented for magnetic resonance (MR) imagery and for digital elevation models. An example of 3-D watershed is also provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

We introduce flat systems, which are equivalent to linear ones via a special type of feedback called endogenous. Their physical properties are subsumed by a linearizing output and they might be regarded as providing another nonlinear extension of Kalman’s controllability. The distance to flatness is measured by a non-negative integer, the defect. We utilize differential algebra which suits well to the fact that, in accordance with Willems ’ standpoint, flatness and defect are best defined without distinguishing between input, state, output and other variables. Many realistic classes of examples are flat. We treat two popular ones: the crane and the car with n trailers, the motion planning of which is obtained via elementary properties of planar curves. The three non-flat examples, the simple, double and variable length pendulums, are borrowed from nonlinear physics. A high frequency control strategy is proposed such that the averaged systems become flat. ∗This work was partially supported by the G.R. “Automatique ” of the CNRS and by the D.R.E.D. of the “Ministère de l’Éducation Nationale”. 1 1

HiC-Pro is an optimized and flexible pipeline for processing Hi-C data from raw reads to normalized contact maps. HiC-Pro maps reads, detects valid ligation products, performs quality controls and generates intra- and inter-chromosomal contact maps. It includes a fast implementation of the iterative correction method and is based on a memory-efficient data format for Hi-C contact maps. In addition, HiC-Pro can use phased genotype data to build allele-specific contact maps. We applied HiC-Pro to different Hi-C datasets, demonstrating its ability to easily process large data in a reasonable time. Source code and documentation are available at http://github.com/nservant/HiC-Pro .

Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. Exposures: BRCA1/2 mutations, family cancer history, and mutation location. Main Outcomes and Measures: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Results: Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and Relevance: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

We report on a search for particle dark matter with the XENON100 experiment, operated at the Laboratori Nazionali del Gran Sasso for 13 months during 2011 and 2012. XENON100 features an ultralow electromagnetic background of $(5.3\ifmmode\pm\else\textpm\fi{}0.6)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\text{ }\text{ }\mathrm{events}/({\mathrm{keV}}_{\mathrm{ee}}\ifmmode\times\else\texttimes\fi{}\mathrm{kg}\ifmmode\times\else\texttimes\fi{}\mathrm{day})$ in the energy region of interest. A blind analysis of $224.6\text{ }\mathrm{\text{live days}}\ifmmode\times\else\texttimes\fi{}34\text{ }\text{ }\mathrm{kg}$ exposure has yielded no evidence for dark matter interactions. The two candidate events observed in the predefined nuclear recoil energy range of $6.6--30.5\text{ }\text{ }{\mathrm{keV}}_{\mathrm{nr}}$ are consistent with the background expectation of ($1.0\ifmmode\pm\else\textpm\fi{}0.2$) events. A profile likelihood analysis using a $6.6--43.3\text{ }\text{ }{\mathrm{keV}}_{\mathrm{nr}}$ energy range sets the most stringent limit on the spin-independent elastic weakly interacting massive particle--nucleon scattering cross section for weakly interacting massive particle masses above $8\text{ }\text{ }\mathrm{GeV}/{c}^{2}$, with a minimum of $2\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}45}\text{ }\text{ }{\mathrm{cm}}^{2}$ at $55\text{ }\text{ }\mathrm{GeV}/{c}^{2}$ and 90% confidence level.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

The Messidor database, which contains hundreds of eye fundus images, has been publicly distributed since 2008. It was created by the Messidor project in order to evaluate automatic lesion segmentation and diabetic retinopathy grading methods. Designing, producing and maintaining such a database entails significant costs. By publicly sharing it, one hopes to bring a valuable resource to the public research community. However, the real interest and benefit of the research community is not easy to quantify. We analyse here the feedback on the Messidor database, after more than 6 years of diffusion. This analysis should apply to other similar research databases.

Science studies has often been against the normative dimension of epistemology, which made a naturalistic study of science impossible. But this is not to say that a new type of normativity cannot be detected at work inscience studies. This is especially true in the second wave of studies dealing with the body, which has aimed at criticizing the physicalization of the body without falling into the various traps of a phenomenology simply added to a physical substrate. This article explores the work of Isabelle Stengers and Vinciane Despret in that respect, and shows how it can be used to rethink the articulation between the various levels that make up a body.

How to address empirically the calculative character of markets without dissolving it? In our paper, we propose a theoretical framework that helps to deal with markets without suspending their calculative properties. In the first section, we construct a broad definition of calculation, grounded on the anthropology of science and techniques. In the next sections, we apply this definition to three constitutive elements of markets: economic goods, economic agents and economic exchanges. First, we examine the question of the calculability of goods: in order to be calculated, goods must be calculable. In the following section, we introduce the notion of calculative distributed agencies to understand how these calculable goods are actually calculated. Thirdly, we consider the rules and material devices that organize the encounter between (and aggregation of) individual supplies and demands, i.e. the specific organizations that allow for a calculated exchange and a market output. Those three elements define concrete markets as collective organized devices that calculate compromises on the values of goods. In each, we encounter different versions of our broad definition of calculation, which we illustrate with examples, mainly taken from the fields of financial markets and mass retail.

International audience

Many single-cell sequencing technologies are now available, but it is still difficult to apply multiple sequencing technologies to the same single cell. In this paper, we propose an unsupervised manifold alignment algorithm, MMD-MA, for integrating multiple measurements carried out on disjoint aliquots of a given population of cells. Effectively, MMD-MA performs an in silico co-assay by embedding cells measured in different ways into a learned latent space. In the MMD-MA algorithm, single-cell data points from multiple domains are aligned by optimizing an objective function with three components: (1) a maximum mean discrepancy (MMD) term to encourage the differently measured points to have similar distributions in the latent space, (2) a distortion term to preserve the structure of the data between the input space and the latent space, and (3) a penalty term to avoid collapse to a trivial solution. Notably, MMD-MA does not require any correspondence information across data modalities, either between the cells or between the features. Furthermore, MMD-MA’s weak distributional requirements for the domains to be aligned allow the algorithm to integrate heterogeneous types of single cell measures, such as gene expression, DNA accessibility, chromatin organization, methylation, and imaging data. We demonstrate the utility of MMD-MA in simulation experiments and using a real data set involving single-cell gene expression and methylation data.

Pansharpening aims at fusing a multispectral and a panchromatic image, featuring the result of the processing with the spectral resolution of the former and the spatial resolution of the latter. In the last decades, many algorithms addressing this task have been presented in the literature. However, the lack of universally recognized evaluation criteria, available image data sets for benchmarking, and standardized implementations of the algorithms makes a thorough evaluation and comparison of the different pansharpening techniques difficult to achieve. In this paper, the authors attempt to fill this gap by providing a critical description and extensive comparisons of some of the main state-of-the-art pansharpening methods. In greater details, several pansharpening algorithms belonging to the component substitution or multiresolution analysis families are considered. Such techniques are evaluated through the two main protocols for the assessment of pansharpening results, i.e., based on the full- and reduced-resolution validations. Five data sets acquired by different satellites allow for a detailed comparison of the algorithms, characterization of their performances with respect to the different instruments, and consistency of the two validation procedures. In addition, the implementation of all the pansharpening techniques considered in this paper and the framework used for running the simulations, comprising the two validation procedures and the main assessment indexes, are collected in a MATLAB toolbox that is made available to the community.

(1954). Electronic structure of primary solid solutions in metals. Advances in Physics: Vol. 3, No. 12, pp. 446-507.

Sugar beet pulp generated by sugar-refining factories has been shown to be an effective adsorbent for the removal of heavy metals from aqueous solutions. The structural components related to the metallic adsorption being determined, batch adsorption studies were performed for several metal ions, namely, Pb2+, Cu2+, Zn2+, Cd2+, and Ni2+ cations. Two simple kinetic models, that is, pseudo-first- and pseudo-second-order, were tested to investigate the adsorption mechanisms. The kinetic parameters of the models were calculated and discussed. For an 8 x 10(-4) M initial metal concentration, the initial sorption rates (v0) ranged from 0.063 mmol x g(-1) x min(-1) for Pb2+ to 0.275 mmol x g(-1) x min(-1) for Ni2+ ions, in the order Ni2+ > Cd2+ > Zn2+ > Cu2+ > Pb2+. The equilibrium data fitted well with the Langmuir and Freundlich models and showed the following affinity order of the material: Pb2+ > Cu2+ > Zn2+ > Cd2+ > Ni2+. The metal removal was strongly dependent on pH and, to a lesser extent, ionic strength. Ion exchange with Ca2+ ions neutralizing the carboxyl groups of the polysaccharide was found to be the predominant mechanism, added with complexation for Pb2+, Cu2+, and Zn2+ metals.

Industry 4.0 provides new paradigms for the industrial management of SMEs. Supported by a growing number of new technologies, this concept appears more flexible and less expensive than traditional enterprise information systems such as ERP and MES. However, SMEs find themselves ill-equipped to face these new possibilities regarding their production planning and control functions. This paper presents a literature review of existing applied research covering different Industry 4.0 issues with regard to SMEs. Papers are classified according to a new framework which allows identification of the targeted performance objectives, the required managerial capacities and the selected group of technologies for each selected case. Our results show that SMEs do not exploit all the resources for implementing Industry 4.0 and often limit themselves to the adoption of Cloud Computing and the Internet of Things. Likewise, SMEs seem to have adopted Industry 4.0 concepts only for monitoring industrial processes and there is still absence of real applications in the field of production planning. Finally, our literature review shows that reported Industry 4.0 projects in SMEs remained cost-driven initiatives and there in still no evidence of real business model transformation at this time.

SUMMARY: More and more cancer studies use next-generation sequencing (NGS) data to detect various types of genomic variation. However, even when researchers have such data at hand, single-nucleotide polymorphism arrays have been considered necessary to assess copy number alterations and especially loss of heterozygosity (LOH). Here, we present the tool Control-FREEC that enables automatic calculation of copy number and allelic content profiles from NGS data, and consequently predicts regions of genomic alteration such as gains, losses and LOH. Taking as input aligned reads, Control-FREEC constructs copy number and B-allele frequency profiles. The profiles are then normalized, segmented and analyzed in order to assign genotype status (copy number and allelic content) to each genomic region. When a matched normal sample is provided, Control-FREEC discriminates somatic from germline events. Control-FREEC is able to analyze overdiploid tumor samples and samples contaminated by normal cells. Low mappability regions can be excluded from the analysis using provided mappability tracks. AVAILABILITY: C++ source code is available at: http://bioinfo.curie.fr/projects/freec/ CONTACT: freec@curie.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A detailed overview of current research in kernel methods and their application to computational biology. Modern machine learning techniques are proving to be extremely valuable for the analysis of data in computational biology problems. One branch of machine learning, kernel methods, lends itself particularly well to the difficult aspects of biological data, which include high dimensionality (as in microarray measurements), representation as discrete and structured data (as in DNA or amino acid sequences), and the need to combine heterogeneous sources of information. This book provides a detailed overview of current research in kernel methods and their applications to computational biology. Following three introductory chapters—an introduction to molecular and computational biology, a short review of kernel methods that focuses on intuitive concepts rather than technical details, and a detailed survey of recent applications of kernel methods in computational biology—the book is divided into three sections that reflect three general trends in current research. The first part presents different ideas for the design of kernel functions specifically adapted to various biological data; the second part covers different approaches to learning from heterogeneous data; and the third part offers examples of successful applications of support vector machine methods.

A stabilizing adaptive controller for a nonlinear system depending affinely on some unknown parameters is presented. It is assumed that this system is feedback stabilizable. A key feature of the method is the use of the Lyapunov equation to design the adaptive law. A result on local stability, two different conditions for global stability, and a local result where the initial conditions of the state of the system only are restricted are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Precise predictions of the antineutrino spectra emitted by nuclear reactors is a key ingredient in measurements of reactor neutrino oscillations as well as in recent applications to the surveillance of power plants in the context of nonproliferation of nuclear weapons. We report new calculations including the latest information from nuclear databases and a detailed error budget. The first part of this work is the so-called ab initio approach where the total antineutrino spectrum is built from the sum of all $\ensuremath{\beta}$ branches of all fission products predicted by an evolution code. Systematic effects and missing information in nuclear databases lead to final relative uncertainties in the $10--20%$ range. A prediction of the antineutrino spectrum associated with the fission of $^{238}\mathrm{U}$ is given based on this ab initio method. For the dominant isotopes we developed a more accurate approach combining information from nuclear databases and reference electron spectra associated with the fission of $^{235}\mathrm{U}$, $^{239}\mathrm{Pu}$, and $^{241}\mathrm{Pu}$, measured at Institut Laue-Langevin (ILL) in the 1980s. We show how the anchor point of the measured total $\ensuremath{\beta}$ spectra can be used to suppress the uncertainty in nuclear databases while taking advantage of all the information they contain. We provide new reference antineutrino spectra for $^{235}\mathrm{U}$, $^{239}\mathrm{Pu}$, and $^{241}\mathrm{Pu}$ isotopes in the 2--8 MeV range. While the shapes of the spectra and their uncertainties are comparable to those of the previous analysis of the ILL data, the normalization is shifted by about $+3%$ on average. In the perspective of the reanalysis of past experiments and direct use of these results by upcoming oscillation experiments, we discuss the various sources of errors and their correlations as well as the corrections induced by off-equilibrium effects.

We present a new massively parallel method for computation of first arrival times in arbitrary velocity models. An implementation on conventional sequential computers is also proposed. This method relies on a systematic application of Huygens' principle in the finite difference approximation. Such an approach explicitly takes into account the existence of different propagation modes (transmitted and diffracted body waves, head waves). Local discontinuities of the time gradient in the first arrival time field (e.g., caustics) are built as intersections of locally independent wavefronts. As a consequence, the proposed method provides accurate first traveltimes in the presence of extremely severe, arbitrarily shaped velocity contrasts. Associated with a simple procedure which accurately traces rays in the obtained time field, this method provides a very fast tool for a large spectrum of seismic and seismological problems. We show moreover that this method may also be used to obtain several arrivals at a given receiver, when the model contains reflectors. This possibility significantly extends the domain of potential geophysical applications.