ETH Zurich

Maximum likelihood or restricted maximum likelihood (REML) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled REML criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or REML criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer.

QUANTUM ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). The acronym ESPRESSO stands for opEn Source Package for Research in Electronic Structure, Simulation, and Optimization. It is freely available to researchers around the world under the terms of the GNU General Public License. QUANTUM ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively parallel architectures, and a great effort being devoted to user friendliness. QUANTUM ESPRESSO is evolving towards a distribution of independent and interoperable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes.

PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696-704), PhyML has been widely used (>2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira-Hasegawa-like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from http://www.atgc-montpellier.fr/phyml/.

The authors present a new molecular dynamics algorithm for sampling the canonical distribution. In this approach the velocities of all the particles are rescaled by a properly chosen random factor. The algorithm is formally justified and it is shown that, in spite of its stochastic nature, a quantity can still be defined that remains constant during the evolution. In numerical applications this quantity can be used to measure the accuracy of the sampling. The authors illustrate the properties of this new method on Lennard-Jones and TIP4P water models in the solid and liquid phases. Its performance is excellent and largely independent of the thermostat parameter also with regard to the dynamic properties.

We present the first public version (v0.2) of the open-source and community-developed Python package, Astropy. This package provides core astronomy-related functionality to the community, including support for domain-specific file formats such as flexible image transport system (FITS) files, Virtual Observatory (VO) tables, and common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions. Significant functionality is under activedevelopment, such as a model fitting framework, VO client and server tools, and aperture and point spread function (PSF) photometry tools. The core development team is actively making additions and enhancements to the current code base, and we encourage anyone interested to participate in the development of future Astropy versions.

Count data can be analyzed using generalized linear mixed models when observations are correlated in ways that require random effects. However, count data are often zero-inflated, containing more zeros than would be expected from the typical error distributions. We present a new package, glmmTMB, and compare it to other R packages that fit zero-inflated mixed models. The glmmTMB package fits many types of GLMMs and extensions, including models with continuously distributed responses, but here we focus on count responses. glmmTMB is faster than glmmADMB, MCMCglmm, and brms, and more flexible than INLA and mgcv for zero-inflated modeling. One unique feature of glmmTMB (among packages that fit zero-inflated mixed models) is its ability to estimate the Conway-Maxwell-Poisson distribution parameterized by the mean. Overall, its most appealing features for new users may be the combination of speed, flexibility, and its interface's similarity to lme4.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14 C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

The MATLAB toolbox YALMIP is introduced. It is described how YALMIP can be used to model and solve optimization problems typically occurring in systems and control theory. In this paper, free MATLAB toolbox YALMIP, developed initially to model SDPs and solve these by interfacing eternal solvers. The toolbox makes development of optimization problems in general, and control oriented SDP problems in particular, extremely simple. In fact, learning 3 YALMIP commands is enough for most users to model and solve the optimization problems

Computer vision applications have come to rely increasingly on superpixels in recent years, but it is not always clear what constitutes a good superpixel algorithm. In an effort to understand the benefits and drawbacks of existing methods, we empirically compare five state-of-the-art superpixel algorithms for their ability to adhere to image boundaries, speed, memory efficiency, and their impact on segmentation performance. We then introduce a new superpixel algorithm, simple linear iterative clustering (SLIC), which adapts a k-means clustering approach to efficiently generate superpixels. Despite its simplicity, SLIC adheres to boundaries as well as or better than previous methods. At the same time, it is faster and more memory efficient, improves segmentation performance, and is straightforward to extend to supervoxel generation.

In this paper we study both market risks and nonmarket risks, without complete markets assumption, and discuss methods of measurement of these risks. We present and justify a set of four desirable properties for measures of risk, and call the measures satisfying these properties “coherent.” We examine the measures of risk provided and the related actions required by SPAN, by the SEC/NASD rules, and by quantile‐based methods. We demonstrate the universality of scenario‐based methods for providing coherent measures. We offer suggestions concerning the SEC method. We also suggest a method to repair the failure of subadditivity of quantile‐based methods.

Metal halides perovskites, such as hybrid organic-inorganic CH3NH3PbI3, are newcomer optoelectronic materials that have attracted enormous attention as solution-deposited absorbing layers in solar cells with power conversion efficiencies reaching 20%. Herein we demonstrate a new avenue for halide perovskites by designing highly luminescent perovskite-based colloidal quantum dot materials. We have synthesized monodisperse colloidal nanocubes (4-15 nm edge lengths) of fully inorganic cesium lead halide perovskites (CsPbX3, X = Cl, Br, and I or mixed halide systems Cl/Br and Br/I) using inexpensive commercial precursors. Through compositional modulations and quantum size-effects, the bandgap energies and emission spectra are readily tunable over the entire visible spectral region of 410-700 nm. The photoluminescence of CsPbX3 nanocrystals is characterized by narrow emission line-widths of 12-42 nm, wide color gamut covering up to 140% of the NTSC color standard, high quantum yields of up to 90%, and radiative lifetimes in the range of 1-29 ns. The compelling combination of enhanced optical properties and chemical robustness makes CsPbX3 nanocrystals appealing for optoelectronic applications, particularly for blue and green spectral regions (410-530 nm), where typical metal chalcogenide-based quantum dots suffer from photodegradation.

Evolutionary algorithms (EAs) are often well-suited for optimization problems involving several, often conflicting objectives. Since 1985, various evolutionary approaches to multiobjective optimization have been developed that are capable of searching for multiple solutions concurrently in a single run. However, the few comparative studies of different methods presented up to now remain mostly qualitative and are often restricted to a few approaches. In this paper, four multiobjective EAs are compared quantitatively where an extended 0/1 knapsack problem is taken as a basis. Furthermore, we introduce a new evolutionary approach to multicriteria optimization, the strength Pareto EA (SPEA), that combines several features of previous multiobjective EAs in a unique manner. It is characterized by (a) storing nondominated solutions externally in a second, continuously updated population, (b) evaluating an individual's fitness dependent on the number of external nondominated points that dominate it, (c) preserving population diversity using the Pareto dominance relationship, and (d) incorporating a clustering procedure in order to reduce the nondominated set without destroying its characteristics. The proof-of-principle results obtained on two artificial problems as well as a larger problem, the synthesis of a digital hardware-software multiprocessor system, suggest that SPEA can be very effective in sampling from along the entire Pareto-optimal front and distributing the generated solutions over the tradeoff surface. Moreover, SPEA clearly outperforms the other four multiobjective EAs on the 0/1 knapsack problem.

The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,873 new measurements from 758 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 118 reviews are many that are new or heavily revised, including a new review on Neutrinos in Cosmology.Starting with this edition, the Review is divided into two volumes. Volume 1 includes the Summary Tables and all review articles. Volume 2 consists of the Particle Listings. Review articles that were previously part of the Listings are now included in volume 1.The complete Review (both volumes) is published online on the website of the Particle Data Group (http://pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is also available.The 2018 edition of the Review of Particle Physics should be cited as: M. Tanabashi et al. (Particle Data Group), Phys. Rev. D 98, 030001 (2018).

We present a new open source, extensible and flexible software platform for Bayesian evolutionary analysis called BEAST 2. This software platform is a re-design of the popular BEAST 1 platform to correct structural deficiencies that became evident as the BEAST 1 software evolved. Key among those deficiencies was the lack of post-deployment extensibility. BEAST 2 now has a fully developed package management system that allows third party developers to write additional functionality that can be directly installed to the BEAST 2 analysis platform via a package manager without requiring a new software release of the platform. This package architecture is showcased with a number of recently published new models encompassing birth-death-sampling tree priors, phylodynamics and model averaging for substitution models and site partitioning. A second major improvement is the ability to read/write the entire state of the MCMC chain to/from disk allowing it to be easily shared between multiple instances of the BEAST software. This facilitates checkpointing and better support for multi-processor and high-end computing extensions. Finally, the functionality in new packages can be easily added to the user interface (BEAUti 2) by a simple XML template-based mechanism because BEAST 2 has been re-designed to provide greater integration between the analysis engine and the user interface so that, for example BEAST and BEAUti use exactly the same XML file format.

Abstract Black carbon aerosol plays a unique and important role in Earth's climate system. Black carbon is a type of carbonaceous material with a unique combination of physical properties. This assessment provides an evaluation of black‐carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice. These effects are calculated with climate models, but when possible, they are evaluated with both microphysical measurements and field observations. Predominant sources are combustion related, namely, fossil fuels for transportation, solid fuels for industrial and residential uses, and open burning of biomass. Total global emissions of black carbon using bottom‐up inventory methods are 7500 Gg yr −1 in the year 2000 with an uncertainty range of 2000 to 29000. However, global atmospheric absorption attributable to black carbon is too low in many models and should be increased by a factor of almost 3. After this scaling, the best estimate for the industrial‐era (1750 to 2005) direct radiative forcing of atmospheric black carbon is +0.71 W m −2 with 90% uncertainty bounds of (+0.08, +1.27) W m −2 . Total direct forcing by all black carbon sources, without subtracting the preindustrial background, is estimated as +0.88 (+0.17, +1.48) W m −2 . Direct radiative forcing alone does not capture important rapid adjustment mechanisms. A framework is described and used for quantifying climate forcings, including rapid adjustments. The best estimate of industrial‐era climate forcing of black carbon through all forcing mechanisms, including clouds and cryosphere forcing, is +1.1 W m −2 with 90% uncertainty bounds of +0.17 to +2.1 W m −2 . Thus, there is a very high probability that black carbon emissions, independent of co‐emitted species, have a positive forcing and warm the climate. We estimate that black carbon, with a total climate forcing of +1.1 W m −2 , is the second most important human emission in terms of its climate forcing in the present‐day atmosphere; only carbon dioxide is estimated to have a greater forcing. Sources that emit black carbon also emit other short‐lived species that may either cool or warm climate. Climate forcings from co‐emitted species are estimated and used in the framework described herein. When the principal effects of short‐lived co‐emissions, including cooling agents such as sulfur dioxide, are included in net forcing, energy‐related sources (fossil fuel and biofuel) have an industrial‐era climate forcing of +0.22 (−0.50 to +1.08) W m −2 during the first year after emission. For a few of these sources, such as diesel engines and possibly residential biofuels, warming is strong enough that eliminating all short‐lived emissions from these sources would reduce net climate forcing (i.e., produce cooling). When open burning emissions, which emit high levels of organic matter, are included in the total, the best estimate of net industrial‐era climate forcing by all short‐lived species from black‐carbon‐rich sources becomes slightly negative (−0.06 W m −2 with 90% uncertainty bounds of −1.45 to +1.29 W m −2 ). The uncertainties in net climate forcing from black‐carbon‐rich sources are substantial, largely due to lack of knowledge about cloud interactions with both black carbon and co‐emitted organic carbon. In prioritizing potential black‐carbon mitigation actions, non‐science factors, such as technical feasibility, costs, policy design, and implementation feasibility play important roles. The major sources of black carbon are presently in different stages with regard to the feasibility for near‐term mitigation. This assessment, by evaluating the large number and complexity of the associated physical and radiative processes in black‐carbon climate forcing, sets a baseline from which to improve future climate forcing estimates.

Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.

Algorithms that must deal with complicated global functions of many variables often exploit the manner in which the given functions factor as a product of "local" functions, each of which depends on a subset of the variables. Such a factorization can be visualized with a bipartite graph that we call a factor graph, In this tutorial paper, we present a generic message-passing algorithm, the sum-product algorithm, that operates in a factor graph. Following a single, simple computational rule, the sum-product algorithm computes-either exactly or approximately-various marginal functions derived from the global function. A wide variety of algorithms developed in artificial intelligence, signal processing, and digital communications can be derived as specific instances of the sum-product algorithm, including the forward/backward algorithm, the Viterbi algorithm, the iterative "turbo" decoding algorithm, Pearl's (1988) belief propagation algorithm for Bayesian networks, the Kalman filter, and certain fast Fourier transform (FFT) algorithms.

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

We present new global maps of the Köppen-Geiger climate classification at an unprecedented 1-km resolution for the present-day (1980-2016) and for projected future conditions (2071-2100) under climate change. The present-day map is derived from an ensemble of four high-resolution, topographically-corrected climatic maps. The future map is derived from an ensemble of 32 climate model projections (scenario RCP8.5), by superimposing the projected climate change anomaly on the baseline high-resolution climatic maps. For both time periods we calculate confidence levels from the ensemble spread, providing valuable indications of the reliability of the classifications. The new maps exhibit a higher classification accuracy and substantially more detail than previous maps, particularly in regions with sharp spatial or elevation gradients. We anticipate the new maps will be useful for numerous applications, including species and vegetation distribution modeling. The new maps including the associated confidence maps are freely available via www.gloh2o.org/koppen.