@article{1849, abstract = {Cell polarity is a fundamental property of pro- and eukaryotic cells. It is necessary for coordination of cell division, cell morphogenesis and signaling processes. How polarity is generated and maintained is a complex issue governed by interconnected feed-back regulations between small GTPase signaling and membrane tension-based signaling that controls membrane trafficking, and cytoskeleton organization and dynamics. Here, we will review the potential role for calcium as a crucial signal that connects and coordinates the respective processes during polarization processes in plants. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.}, author = {Himschoot, Ellie and Beeckman, Tom and Friml, Jiřĺ and Vanneste, Steffen}, journal = {Biochimica et Biophysica Acta - Molecular Cell Research}, number = {9}, pages = {2168 -- 2172}, publisher = {Elsevier}, title = {{Calcium is an organizer of cell polarity in plants}}, doi = {10.1016/j.bbamcr.2015.02.017}, volume = {1853}, year = {2015}, } @article{1850, abstract = {Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels.}, author = {Novak, Sebastian and Cremer, Sylvia}, journal = {Journal of Theoretical Biology}, number = {5}, pages = {54 -- 64}, publisher = {Elsevier}, title = {{Fungal disease dynamics in insect societies: Optimal killing rates and the ambivalent effect of high social interaction rates}}, doi = {10.1016/j.jtbi.2015.02.018}, volume = {372}, year = {2015}, } @article{1851, abstract = {We consider mating strategies for females who search for males sequentially during a season of limited length. We show that the best strategy rejects a given male type if encountered before a time-threshold but accepts him after. For frequency-independent benefits, we obtain the optimal time-thresholds explicitly for both discrete and continuous distributions of males, and allow for mistakes being made in assessing the correct male type. When the benefits are indirect (genes for the offspring) and the population is under frequency-dependent ecological selection, the benefits depend on the mating strategy of other females as well. This case is particularly relevant to speciation models that seek to explore the stability of reproductive isolation by assortative mating under frequency-dependent ecological selection. We show that the indirect benefits are to be quantified by the reproductive values of couples, and describe how the evolutionarily stable time-thresholds can be found. We conclude with an example based on the Levene model, in which we analyze the evolutionarily stable assortative mating strategies and the strength of reproductive isolation provided by them.}, author = {Priklopil, Tadeas and Kisdi, Eva and Gyllenberg, Mats}, issn = {1558-5646}, journal = {Evolution}, number = {4}, pages = {1015 -- 1026}, publisher = {Wiley}, title = {{Evolutionarily stable mating decisions for sequentially searching females and the stability of reproductive isolation by assortative mating}}, doi = {10.1111/evo.12618}, volume = {69}, year = {2015}, } @article{1855, abstract = {Summary: Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.}, author = {Mcmahon, Dino and Fürst, Matthias and Caspar, Jesicca and Theodorou, Panagiotis and Brown, Mark and Paxton, Robert}, journal = {Journal of Animal Ecology}, number = {3}, pages = {615 -- 624}, publisher = {Wiley}, title = {{A sting in the spit: Widespread cross-infection of multiple RNA viruses across wild and managed bees}}, doi = {10.1111/1365-2656.12345}, volume = {84}, year = {2015}, } @article{1856, abstract = {The traditional synthesis question given a specification asks for the automatic construction of a system that satisfies the specification, whereas often there exists a preference order among the different systems that satisfy the given specification. Under a probabilistic assumption about the possible inputs, such a preference order is naturally expressed by a weighted automaton, which assigns to each word a value, such that a system is preferred if it generates a higher expected value. We solve the following optimal synthesis problem: given an omega-regular specification, a Markov chain that describes the distribution of inputs, and a weighted automaton that measures how well a system satisfies the given specification under the input assumption, synthesize a system that optimizes the measured value. For safety specifications and quantitative measures that are defined by mean-payoff automata, the optimal synthesis problem reduces to finding a strategy in a Markov decision process (MDP) that is optimal for a long-run average reward objective, which can be achieved in polynomial time. For general omega-regular specifications along with mean-payoff automata, the solution rests on a new, polynomial-time algorithm for computing optimal strategies in MDPs with mean-payoff parity objectives. Our algorithm constructs optimal strategies that consist of two memoryless strategies and a counter. The counter is in general not bounded. To obtain a finite-state system, we show how to construct an ε-optimal strategy with a bounded counter, for all ε > 0. Furthermore, we show how to decide in polynomial time if it is possible to construct an optimal finite-state system (i.e., a system without a counter) for a given specification. We have implemented our approach and the underlying algorithms in a tool that takes qualitative and quantitative specifications and automatically constructs a system that satisfies the qualitative specification and optimizes the quantitative specification, if such a system exists. We present some experimental results showing optimal systems that were automatically generated in this way.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara and Singh, Rohit}, journal = {Journal of the ACM}, number = {1}, publisher = {ACM}, title = {{Measuring and synthesizing systems in probabilistic environments}}, doi = {10.1145/2699430}, volume = {62}, year = {2015}, } @inproceedings{1857, abstract = {Sharing information between multiple tasks enables algorithms to achieve good generalization performance even from small amounts of training data. However, in a realistic scenario of multi-task learning not all tasks are equally related to each other, hence it could be advantageous to transfer information only between the most related tasks. In this work we propose an approach that processes multiple tasks in a sequence with sharing between subsequent tasks instead of solving all tasks jointly. Subsequently, we address the question of curriculum learning of tasks, i.e. finding the best order of tasks to be learned. Our approach is based on a generalization bound criterion for choosing the task order that optimizes the average expected classification performance over all tasks. Our experimental results show that learning multiple related tasks sequentially can be more effective than learning them jointly, the order in which tasks are being solved affects the overall performance, and that our model is able to automatically discover the favourable order of tasks. }, author = {Pentina, Anastasia and Sharmanska, Viktoriia and Lampert, Christoph}, location = {Boston, MA, United States}, pages = {5492 -- 5500}, publisher = {IEEE}, title = {{Curriculum learning of multiple tasks}}, doi = {10.1109/CVPR.2015.7299188}, year = {2015}, } @inproceedings{1858, abstract = {We study the problem of predicting the future, though only in the probabilistic sense of estimating a future state of a time-varying probability distribution. This is not only an interesting academic problem, but solving this extrapolation problem also has many practical application, e.g. for training classifiers that have to operate under time-varying conditions. Our main contribution is a method for predicting the next step of the time-varying distribution from a given sequence of sample sets from earlier time steps. For this we rely on two recent machine learning techniques: embedding probability distributions into a reproducing kernel Hilbert space, and learning operators by vector-valued regression. We illustrate the working principles and the practical usefulness of our method by experiments on synthetic and real data. We also highlight an exemplary application: training a classifier in a domain adaptation setting without having access to examples from the test time distribution at training time.}, author = {Lampert, Christoph}, location = {Boston, MA, United States}, pages = {942 -- 950}, publisher = {IEEE}, title = {{Predicting the future behavior of a time-varying probability distribution}}, doi = {10.1109/CVPR.2015.7298696}, year = {2015}, } @inproceedings{1859, abstract = {Structural support vector machines (SSVMs) are amongst the best performing models for structured computer vision tasks, such as semantic image segmentation or human pose estimation. Training SSVMs, however, is computationally costly, because it requires repeated calls to a structured prediction subroutine (called \emph{max-oracle}), which has to solve an optimization problem itself, e.g. a graph cut. In this work, we introduce a new algorithm for SSVM training that is more efficient than earlier techniques when the max-oracle is computationally expensive, as it is frequently the case in computer vision tasks. The main idea is to (i) combine the recent stochastic Block-Coordinate Frank-Wolfe algorithm with efficient hyperplane caching, and (ii) use an automatic selection rule for deciding whether to call the exact max-oracle or to rely on an approximate one based on the cached hyperplanes. We show experimentally that this strategy leads to faster convergence to the optimum with respect to the number of requires oracle calls, and that this translates into faster convergence with respect to the total runtime when the max-oracle is slow compared to the other steps of the algorithm. }, author = {Shah, Neel and Kolmogorov, Vladimir and Lampert, Christoph}, location = {Boston, MA, USA}, pages = {2737 -- 2745}, publisher = {IEEE}, title = {{A multi-plane block-coordinate Frank-Wolfe algorithm for training structural SVMs with a costly max-oracle}}, doi = {10.1109/CVPR.2015.7298890}, year = {2015}, } @inproceedings{1860, abstract = {Classifiers for object categorization are usually evaluated by their accuracy on a set of i.i.d. test examples. This provides us with an estimate of the expected error when applying the classifiers to a single new image. In real application, however, classifiers are rarely only used for a single image and then discarded. Instead, they are applied sequentially to many images, and these are typically not i.i.d. samples from a fixed data distribution, but they carry dependencies and their class distribution varies over time. In this work, we argue that the phenomenon of correlated data at prediction time is not a nuisance, but a blessing in disguise. We describe a probabilistic method for adapting classifiers at prediction time without having to retrain them. We also introduce a framework for creating realistically distributed image sequences, which offers a way to benchmark classifier adaptation methods, such as the one we propose. Experiments on the ILSVRC2010 and ILSVRC2012 datasets show that adapting object classification systems at prediction time can significantly reduce their error rate, even with no additional human feedback.}, author = {Royer, Amélie and Lampert, Christoph}, location = {Boston, MA, United States}, pages = {1401 -- 1409}, publisher = {IEEE}, title = {{Classifier adaptation at prediction time}}, doi = {10.1109/CVPR.2015.7298746}, year = {2015}, } @article{1861, abstract = {Continuous-time Markov chains are commonly used in practice for modeling biochemical reaction networks in which the inherent randomness of themolecular interactions cannot be ignored. This has motivated recent research effort into methods for parameter inference and experiment design for such models. The major difficulty is that such methods usually require one to iteratively solve the chemical master equation that governs the time evolution of the probability distribution of the system. This, however, is rarely possible, and even approximation techniques remain limited to relatively small and simple systems. An alternative explored in this article is to base methods on only some low-order moments of the entire probability distribution. We summarize the theory behind such moment-based methods for parameter inference and experiment design and provide new case studies where we investigate their performance.}, author = {Ruess, Jakob and Lygeros, John}, journal = {ACM Transactions on Modeling and Computer Simulation}, number = {2}, publisher = {ACM}, title = {{Moment-based methods for parameter inference and experiment design for stochastic biochemical reaction networks}}, doi = {10.1145/2688906}, volume = {25}, year = {2015}, } @article{1864, abstract = {The Altshuler–Shklovskii formulas (Altshuler and Shklovskii, BZh Eksp Teor Fiz 91:200, 1986) predict, for any disordered quantum system in the diffusive regime, a universal power law behaviour for the correlation functions of the mesoscopic eigenvalue density. In this paper and its companion (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013), we prove these formulas for random band matrices. In (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013) we introduced a diagrammatic approach and presented robust estimates on general diagrams under certain simplifying assumptions. In this paper, we remove these assumptions by giving a general estimate of the subleading diagrams. We also give a precise analysis of the leading diagrams which give rise to the Altschuler–Shklovskii power laws. Moreover, we introduce a family of general random band matrices which interpolates between real symmetric (β = 1) and complex Hermitian (β = 2) models, and track the transition for the mesoscopic density–density correlation. Finally, we address the higher-order correlation functions by proving that they behave asymptotically according to a Gaussian process whose covariance is given by the Altshuler–Shklovskii formulas. }, author = {Erdös, László and Knowles, Antti}, journal = {Annales Henri Poincare}, number = {3}, pages = {709 -- 799}, publisher = {Springer}, title = {{The Altshuler–Shklovskii formulas for random band matrices II: The general case}}, doi = {10.1007/s00023-014-0333-5}, volume = {16}, year = {2015}, } @article{1865, abstract = {The plant hormone auxin and its directional transport are known to play a crucial role in defining the embryonic axis and subsequent development of the body plan. Although the role of PIN auxin efflux transporters has been clearly assigned during embryonic shoot and root specification, the role of the auxin influx carriers AUX1 and LIKE-AUX1 (LAX) proteins is not well established. Here, we used chemical and genetic tools on Brassica napus microspore-derived embryos and Arabidopsis thaliana zygotic embryos, and demonstrate that AUX1, LAX1 and LAX2 are required for both shoot and root pole formation, in concert with PIN efflux carriers. Furthermore, we uncovered a positive-feedback loop betweenMONOPTEROS(ARF5)-dependent auxin signalling and auxin transport. ThisMONOPTEROSdependent transcriptional regulation of auxin influx (AUX1, LAX1 and LAX2) and auxin efflux (PIN1 and PIN4) carriers by MONOPTEROS helps to maintain proper auxin transport to the root tip. These results indicate that auxin-dependent cell specification during embryo development requires balanced auxin transport involving both influx and efflux mechanisms, and that this transport is maintained by a positive transcriptional feedback on auxin signalling.}, author = {Robert, Hélène and Grunewald, Wim and Sauer, Michael and Cannoot, Bernard and Soriano, Mercedes and Swarup, Ranjan and Weijers, Dolf and Bennett, Malcolm and Boutilier, Kim and Friml, Jirí}, journal = {Development}, number = {4}, pages = {702 -- 711}, publisher = {Company of Biologists}, title = {{Plant embryogenesis requires AUX/LAX-mediated auxin influx}}, doi = {10.1242/dev.115832}, volume = {142}, year = {2015}, } @article{1866, author = {Henzinger, Thomas A and Raskin, Jean}, journal = {Communications of the ACM}, number = {2}, pages = {86--86}, publisher = {ACM}, title = {{The equivalence problem for finite automata: Technical perspective}}, doi = {10.1145/2701001}, volume = {58}, year = {2015}, } @article{1867, abstract = {Cultured mammalian cells essential are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are critical for cellular redox reactions and sense light in naturally occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We first compared three procedures for extraction of free and noncovalently protein-bound flavins and verified extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established, and detection was performed by LED-induced fluorescence with limit of detections (LODs 0.5-3.8 nM). We found that riboflavin (RF), FMN, and FAD contents varied significantly between cell lines. RF (3.1-14 amol/cell) and FAD (2.2-17.0 amol/cell) were the predominant flavins, while FMN (0.46-3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of RF were detected that were not described previously. Quantification of flavins in mammalian cell lines will allow a better understanding of cellular redox reactions and optogenetic tools.}, author = {Hühner, Jens and Inglés Prieto, Álvaro and Neusüß, Christian and Lämmerhofer, Michael and Janovjak, Harald L}, journal = {Electrophoresis}, number = {4}, pages = {518 -- 525}, publisher = {Wiley}, title = {{Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection}}, doi = {10.1002/elps.201400451}, volume = {36}, year = {2015}, } @article{1868, abstract = {We investigate high-dimensional nonlinear dynamical systems exhibiting multiple resonances under adiabatic parameter variations. Our motivations come from experimental considerations where time-dependent sweeping of parameters is a practical approach to probing and characterizing the bifurcations of the system. The question is whether bifurcations so detected are faithful representations of the bifurcations intrinsic to the original stationary system. Utilizing a harmonically forced, closed fluid flow system that possesses multiple resonances and solving the Navier-Stokes equation under proper boundary conditions, we uncover the phenomenon of the early effect. Specifically, as a control parameter, e.g., the driving frequency, is adiabatically increased from an initial value, resonances emerge at frequency values that are lower than those in the corresponding stationary system. The phenomenon is established by numerical characterization of physical quantities through the resonances, which include the kinetic energy and the vorticity field, and a heuristic analysis based on the concept of instantaneous frequency. A simple formula is obtained which relates the resonance points in the time-dependent and time-independent systems. Our findings suggest that, in general, any true bifurcation of a nonlinear dynamical system can be unequivocally uncovered through adiabatic parameter sweeping, in spite of a shift in the bifurcation point, which is of value to experimental studies of nonlinear dynamical systems.}, author = {Park, Youngyong and Do, Younghae and Altmeyer, Sebastian and Lai, Yingcheng and Lee, Gyuwon}, issn = {1539-3755}, journal = {Physical Review E}, number = {2}, publisher = {American Physical Society}, title = {{Early effect in time-dependent, high-dimensional nonlinear dynamical systems with multiple resonances}}, doi = {10.1103/PhysRevE.91.022906}, volume = {91}, year = {2015}, } @article{1871, abstract = {The plant hormone auxin is a key regulator of plant growth and development. Differences in auxin distribution within tissues are mediated by the polar auxin transport machinery, and cellular auxin responses occur depending on changes in cellular auxin levels. Multiple receptor systems at the cell surface and in the interior operate to sense and interpret fluctuations in auxin distribution that occur during plant development. Until now, three proteins or protein complexes that can bind auxin have been identified. SCFTIR1 [a SKP1-cullin-1-F-box complex that contains transport inhibitor response 1 (TIR1) as the F-box protein] and S-phase-kinaseassociated protein 2 (SKP2) localize to the nucleus, whereas auxinbinding protein 1 (ABP1), predominantly associates with the endoplasmic reticulum and cell surface. In this Cell Science at a Glance article, we summarize recent discoveries in the field of auxin transport and signaling that have led to the identification of new components of these pathways, as well as their mutual interaction.}, author = {Grones, Peter and Friml, Jirí}, journal = {Journal of Cell Science}, number = {1}, pages = {1 -- 7}, publisher = {Company of Biologists}, title = {{Auxin transporters and binding proteins at a glance}}, doi = {10.1242/jcs.159418}, volume = {128}, year = {2015}, } @article{1873, abstract = {We consider partially observable Markov decision processes (POMDPs) with limit-average payoff, where a reward value in the interval [0,1] is associated with every transition, and the payoff of an infinite path is the long-run average of the rewards. We consider two types of path constraints: (i) a quantitative constraint defines the set of paths where the payoff is at least a given threshold λ1ε(0,1]; and (ii) a qualitative constraint which is a special case of the quantitative constraint with λ1=1. We consider the computation of the almost-sure winning set, where the controller needs to ensure that the path constraint is satisfied with probability 1. Our main results for qualitative path constraints are as follows: (i) the problem of deciding the existence of a finite-memory controller is EXPTIME-complete; and (ii) the problem of deciding the existence of an infinite-memory controller is undecidable. For quantitative path constraints we show that the problem of deciding the existence of a finite-memory controller is undecidable. We also present a prototype implementation of our EXPTIME algorithm and experimental results on several examples.}, author = {Chatterjee, Krishnendu and Chmelik, Martin}, journal = {Artificial Intelligence}, pages = {46 -- 72}, publisher = {Elsevier}, title = {{POMDPs under probabilistic semantics}}, doi = {10.1016/j.artint.2014.12.009}, volume = {221}, year = {2015}, } @article{1874, abstract = {The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource.}, author = {Boccara, Charlotte and Kjønigsen, Lisa and Hammer, Ingvild and Bjaalie, Jan and Leergaard, Trygve and Witter, Menno}, journal = {Hippocampus}, number = {7}, pages = {838 -- 857}, publisher = {Wiley}, title = {{A three-plane architectonic atlas of the rat hippocampal region}}, doi = {10.1002/hipo.22407}, volume = {25}, year = {2015}, } @article{1878, abstract = {Petrocoptis is a small genus of chasmophytic plants endemic to the Iberian Peninsula, with some localized populations in the French Pyrenees. Within the genus, a dozen species have been recognized based on morphological diversity, most of them with limited distribution area, in small populations and frequently with potential threats to their survival. To date, however, a molecular evaluation of the current systematic treatments has not been carried out. The aim of the present study is to infer phylogenetic relationships among its subordinate taxa by using plastidial rps16 intron and nuclear internal transcribed spacer (ITS) DNA sequences; and evaluate the phylogenetic placement of the genus Petrocoptis within the family Caryophyllaceae. The monophyly of Petrocoptis is supported by both ITS and rps16 intron sequence analyses. Furthermore, time estimates using BEAST analyses indicate a Middle to Late Miocene diversification (10.59 Myr, 6.44–15.26 Myr highest posterior densities [HPD], for ITS; 14.30 Myr, 8.61–21.00 Myr HPD, for rps16 intron).}, author = {Cires Rodriguez, Eduardo and Prieto, José}, journal = {Journal of Plant Research}, number = {2}, pages = {223 -- 238}, publisher = {Springer}, title = {{Phylogenetic relationships of Petrocoptis A. Braun ex Endl. (Caryophyllaceae), a discussed genus from the Iberian Peninsula}}, doi = {10.1007/s10265-014-0691-6}, volume = {128}, year = {2015}, } @article{1879, abstract = {When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions.}, author = {Kremer, A and Lippens, Stefaan and Bartunkova, Sonia and Asselbergh, Bob and Blanpain, Cendric and Fendrych, Matyas and Goossens, A and Holt, Matthew and Janssens, Sophie and Krols, Michiel and Larsimont, Jean and Mc Guire, Conor and Nowack, Moritz and Saelens, Xavier and Schertel, Andreas and Schepens, B and Slezak, M and Timmerman, Vincent and Theunis, Clara and Van Brempt, Ronald and Visser, Y and Guérin, Christophe}, journal = {Journal of Microscopy}, number = {2}, pages = {80 -- 96}, publisher = {Wiley-Blackwell}, title = {{Developing 3D SEM in a broad biological context}}, doi = {10.1111/jmi.12211}, volume = {259}, year = {2015}, }