@article{826, abstract = {Plants exhibit a unique developmental flexibility to ever-changing environmental conditions. To achieve their profound adaptability, plants are able to maintain permanent stem cell populations and form new organs during the entire plant life cycle. Signaling substances, called plant hormones, such as auxin, cytokinin, abscisic acid, brassinosteroid, ethylene, gibberellin, jasmonic acid, and strigolactone, govern and coordinate these developmental processes. Physiological and genetic studies have dissected the molecular components of signal perception and transduction of the individual hormonal pathways. However, over recent years it has become evident that hormones do not act only in a linear pathway. Hormonal pathways are interconnected by a complex network of interactions and feedback circuits that determines the final outcome of the individual hormone actions. This raises questions about the molecular mechanisms underlying hormonal cross talk and about how these hormonal networks are established, maintained, and modulated throughout plant development.}, author = {Vanstraelen, Marleen and Eva Benková}, journal = {Annual Review of Cell and Developmental Biology}, pages = {463 -- 487}, publisher = {Annual Reviews}, title = {{Hormonal interactions in the regulation of plant development}}, doi = {10.1146/annurev-cellbio-101011-155741}, volume = {28}, year = {2012}, } @article{829, abstract = {The architecture of a plant's root system, established postembryonically, results from both coordinated root growth and lateral root branching. The plant hormones auxin and cytokinin are central endogenous signaling molecules that regulate lateral root organogenesis positively and negatively, respectively. Tight control and mutual balance of their antagonistic activities are particularly important during the early phases of lateral root organogenesis to ensure continuous lateral root initiation (LRI) and proper development of lateral root primordia (LRP). Here, we show that the early phases of lateral root organogenesis, including priming and initiation, take place in root zones with a repressed cytokinin response. Accordingly, ectopic overproduction of cytokinin in the root basal meristem most efficiently inhibits LRI. Enhanced cytokinin responses in pericycle cells between existing LRP might restrict LRI near existing LRP and, when compromised, ectopic LRI occurs. Furthermore, our results demonstrate that young LRP are more sensitive to perturbations in the cytokinin activity than are developmentally more advanced primordia. We hypothesize that the effect of cytokinin on the development of primordia possibly depends on the robustness and stability of the auxin gradient.}, author = {Bielach, Agnieszka and Podlesakova, Katerina and Peter Marhavy and Duclercq, Jérôme and Candela Cuesta and Muller, Bruno and Grunewald, Wim and Tarkowski, Petr and Eva Benková}, journal = {The Plant Cell}, number = {10}, pages = {3967 -- 3981}, publisher = {American Society of Plant Biologists}, title = {{Spatiotemporal regulation of lateral root organogenesis in Arabidopsis by cytokinin}}, doi = {10.1105/tpc.112.103044}, volume = {24}, year = {2012}, } @article{846, abstract = {Whether or not evolutionary change is inherently irreversible remains a controversial topic. Some examples of evolutionary irreversibility are known; however, this question has not been comprehensively addressed at the molecular level. Here, we use data from 221 human genes with known pathogenic mutations to estimate the rate of irreversibility in protein evolution. For these genes, we reconstruct ancestral amino acid sequences along the mammalian phylogeny and identify ancestral amino acid states that match known pathogenic mutations. Such cases represent inherent evolutionary irreversibility because, at the present moment, reversals to these ancestral amino acid states are impossible for the human lineage. We estimate that approximately 10% of all amino acid substitutions along the mammalian phylogeny are irreversible, such that a return to the ancestral amino acid state would lead to a pathogenic phenotype. For a subset of 51 genes with high rates of irreversibility, as much as 40% of all amino acid evolution was estimated to be irreversible. Because pathogenic phenotypes do not resemble ancestral phenotypes, the molecular nature of the high rate of irreversibility in proteins is best explained by evolution with a high prevalence of compensatory, epistatic interactions between amino acid sites. Under such mode of protein evolution, once an amino acid substitution is fixed, the probability of its reversal declines as the protein sequence accumulates changes that affect the phenotypic manifestation of the ancestral state. The prevalence of epistasis in evolution indicates that the observed high rate of irreversibility in protein evolution is an inherent property of protein structure and function.}, author = {Soylemez, Onuralp and Fyodor Kondrashov}, journal = {Genome Biology and Evolution}, number = {12}, pages = {1213 -- 1222}, publisher = {Oxford University Press}, title = {{Estimating the rate of irreversibility in protein evolution}}, doi = {10.1093/gbe/evs096}, volume = {4}, year = {2012}, } @article{8463, abstract = {The 1H dipolar network, which is the major obstacle for applying proton detection in the solid-state, can be reduced by deuteration, employing the RAP (Reduced Adjoining Protonation) labeling scheme, which yields random protonation at non-exchangeable sites. We present here a systematic study on the optimal degree of random sidechain protonation in RAP samples as a function of the MAS (magic angle spinning) frequency. In particular, we compare 1H sensitivity and linewidth of a microcrystalline protein, the SH3 domain of chicken α-spectrin, for samples, prepared with 5–25 % H2O in the E. coli growth medium, in the MAS frequency range of 20–60 kHz. At an external field of 19.96 T (850 MHz), we find that using a proton concentration between 15 and 25 % in the M9 medium yields the best compromise in terms of sensitivity and resolution, with an achievable average 1H linewidth on the order of 40–50 Hz. Comparing sensitivities at a MAS frequency of 60 versus 20 kHz, a gain in sensitivity by a factor of 4–4.5 is observed in INEPT-based 1H detected 1D 1H,13C correlation experiments. In total, we find that spectra recorded with a 1.3 mm rotor at 60 kHz have almost the same sensitivity as spectra recorded with a fully packed 3.2 mm rotor at 20 kHz, even though ~20× less material is employed. The improved sensitivity is attributed to 1H line narrowing due to fast MAS and to the increased efficiency of the 1.3 mm coil.}, author = {Asami, Sam and Szekely, Kathrin and Schanda, Paul and Meier, Beat H. and Reif, Bernd}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, number = {2}, pages = {155--168}, publisher = {Springer Nature}, title = {{Optimal degree of protonation for 1H detection of aliphatic sites in randomly deuterated proteins as a function of the MAS frequency}}, doi = {10.1007/s10858-012-9659-9}, volume = {54}, year = {2012}, } @article{8465, abstract = {We demonstrate that conformational exchange processes in proteins on microsecond-to-millisecond time scales can be detected and quantified by solid-state NMR spectroscopy. We show two independent approaches that measure the effect of conformational exchange on transverse relaxation parameters, namely Carr–Purcell–Meiboom–Gill relaxation-dispersion experiments and measurement of differential multiple-quantum coherence decay. Long coherence lifetimes, as required for these experiments, are achieved by the use of highly deuterated samples and fast magic-angle spinning. The usefulness of the approaches is demonstrated by application to microcrystalline ubiquitin. We detect a conformational exchange process in a region of the protein for which dynamics have also been observed in solution. Interestingly, quantitative analysis of the data reveals that the exchange process is more than 1 order of magnitude slower than in solution, and this points to the impact of the crystalline environment on free energy barriers.}, author = {Tollinger, Martin and Sivertsen, Astrid C. and Meier, Beat H. and Ernst, Matthias and Schanda, Paul}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {36}, pages = {14800--14807}, publisher = {American Chemical Society}, title = {{Site-resolved measurement of microsecond-to-millisecond conformational-exchange processes in proteins by solid-state NMR spectroscopy}}, doi = {10.1021/ja303591y}, volume = {134}, year = {2012}, } @article{8466, abstract = {Recent advances in NMR spectroscopy and the availability of high magnetic field strengths now offer the possibility to record real-time 3D NMR spectra of short-lived protein states, e.g., states that become transiently populated during protein folding. Here we present a strategy for obtaining sequential NMR assignments as well as atom-resolved information on structural and dynamic features within a folding intermediate of the amyloidogenic protein β2-microglobulin that has a half-lifetime of only 20 min.}, author = {Rennella, Enrico and Cutuil, Thomas and Schanda, Paul and Ayala, Isabel and Forge, Vincent and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {8066--8069}, publisher = {American Chemical Society}, title = {{Real-time NMR characterization of structure and dynamics in a transiently populated protein folding intermediate}}, doi = {10.1021/ja302598j}, volume = {134}, year = {2012}, } @article{8467, abstract = {Partial deuteration is a powerful tool to increase coherence life times and spectral resolution in proton solid-state NMR. The J coupling to deuterium needs, however, to be decoupled to maintain the good resolution in the (usually indirect) 13C dimension(s). We present a simple and reversible way to expand a commercial 1.3 mm HCN MAS probe with a 2H channel with sufficient field strength for J-decoupling of deuterium, namely 2–3 kHz. The coil is placed at the outside of the stator and requires no significant modifications to the probe. The performance and the realizable gains in sensitivity and resolution are demonstrated using perdeuterated ubiquitin, with selectively CHD2-labeled methyl groups.}, author = {Huber, Matthias and With, Oliver and Schanda, Paul and Verel, René and Ernst, Matthias and Meier, Beat H.}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, pages = {76--80}, publisher = {Elsevier}, title = {{A supplementary coil for 2H decoupling with commercial HCN MAS probes}}, doi = {10.1016/j.jmr.2011.10.010}, volume = {214}, year = {2012}, } @article{8502, abstract = {The famous ergodic hypothesis suggests that for a typical Hamiltonian on a typical energy surface nearly all trajectories are dense. KAM theory disproves it. Ehrenfest (The Conceptual Foundations of the Statistical Approach in Mechanics. Ithaca, NY: Cornell University Press, 1959) and Birkhoff (Collected Math Papers. Vol 2, New York: Dover, pp 462–465, 1968) stated the quasi-ergodic hypothesis claiming that a typical Hamiltonian on a typical energy surface has a dense orbit. This question is wide open. Herman (Proceedings of the International Congress of Mathematicians, Vol II (Berlin, 1998). Doc Math 1998, Extra Vol II, Berlin: Int Math Union, pp 797–808, 1998) proposed to look for an example of a Hamiltonian near H0(I)=⟨I,I⟩2 with a dense orbit on the unit energy surface. In this paper we construct a Hamiltonian H0(I)+εH1(θ,I,ε) which has an orbit dense in a set of maximal Hausdorff dimension equal to 5 on the unit energy surface.}, author = {Kaloshin, Vadim and Saprykina, Maria}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {643--697}, publisher = {Springer Nature}, title = {{An example of a nearly integrable Hamiltonian system with a trajectory dense in a set of maximal Hausdorff dimension}}, doi = {10.1007/s00220-012-1532-x}, volume = {315}, year = {2012}, } @article{858, abstract = {ackground: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.Results: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.Conclusions: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.Reviewers: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers' Comments section.}, author = {Povolotskaya, Inna and Fyodor Kondrashov and Ledda, Alice and Vlasov, Peter K}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Stop codons in bacteria are not selectively equivalent}}, doi = {10.1186/1745-6150-7-30}, volume = {7}, year = {2012}, } @article{900, abstract = {The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.}, author = {Breen, Michael S and Kemena, Carsten and Vlasov, Peter K and Notredame, Cédric and Fyodor Kondrashov}, journal = {Nature}, number = {7421}, pages = {535 -- 538}, publisher = {Nature Publishing Group}, title = {{Epistasis as the primary factor in molecular evolution}}, doi = {10.1038/nature11510}, volume = {490}, year = {2012}, } @article{9014, abstract = {In this Letter, we explore experimentally the phase behavior of a dense active suspension of self-propelled colloids. In addition to a solidlike and gaslike phase observed for high and low densities, a novel cluster phase is reported at intermediate densities. This takes the form of a stationary assembly of dense aggregates—resulting from a permanent dynamical merging and separation of active colloids—whose average size grows with activity as a linear function of the self-propelling velocity. While different possible scenarios can be considered to account for these observations—such as a generic velocity weakening instability recently put forward—we show that the experimental results are reproduced mathematically by a chemotactic aggregation mechanism, originally introduced to account for bacterial aggregation and accounting here for diffusiophoretic chemical interaction between colloidal swimmers.}, author = {Theurkauff, I. and Cottin-Bizonne, C. and Palacci, Jérémie A and Ybert, C. and Bocquet, L.}, issn = {10797114}, journal = {Physical Review Letters}, number = {26}, publisher = {American Physical Society }, title = {{Dynamic clustering in active colloidal suspensions with chemical signaling}}, doi = {10.1103/physrevlett.108.268303}, volume = {108}, year = {2012}, } @article{91, abstract = {We demonstrate how to appropriately estimate the zero-frequency (static) hyperpolarizability of an organic molecule from its charge distribution, and we explore applications of these estimates for identifying and evaluating new organic nonlinear optical (NLO) materials. First, we calculate hyperpolarizabilities from Hartree-Fock-derived charge distributions and find order-of-magnitude agreement with experimental values. We show that these simple arithmetic calculations will enable systematic searches for new organic NLO molecules. Second, we derive hyperpolarizabilities from crystallographic data using a multipolar charge-density analysis and find good agreement with empirical calculations. This demonstrates an experimental determination of the full static hyperpolarizability tensor in a solid-state sample. }, author = {Higginbotham, Andrew P and Cole, Jacqueline and Blood Forsythe, Martin and Hickstein, Daniel}, journal = {Journal of Applied Physics}, number = {3}, publisher = {American Institute of Physics}, title = {{Identifying and evaluating organic nonlinear optical materials via molecular moments}}, doi = {10.1063/1.3678593}, volume = {111}, year = {2012}, } @article{9142, abstract = {In models of radiative–convective equilibrium it is known that convection can spontaneously aggregate into one single localized moist region if the domain is large enough. The large changes in the mean climate state and radiative fluxes accompanying this self-aggregation raise questions as to what simulations at lower resolutions with parameterized convection, in similar homogeneous geometries, should be expected to produce to be considered successful in mimicking a cloud-resolving model. The authors investigate this self-aggregation in a nonrotating, three-dimensional cloud-resolving model on a square domain without large-scale forcing. It is found that self-aggregation is sensitive not only to the domain size, but also to the horizontal resolution. With horizontally homogeneous initial conditions, convective aggregation only occurs on domains larger than about 200km and with resolutions coarser than about 2km in the model examined. The system exhibits hysteresis, so that with aggregated initial conditions, convection remains aggregated even at our finest resolution, 500m, as long as the domain is greater than 200–300km. The sensitivity of self-aggregation to resolution and domain size in this model is due to the sensitivity of the distribution of low clouds to these two parameters. Indeed, the mechanism responsible for the aggregation of convection is the dynamical response to the longwave radiative cooling from low clouds. Strong longwave cooling near cloud top in dry regions forces downward motion, which by continuity generates inflow near cloud top and near-surface outflow from dry regions. This circulation results in the net export of moist static energy from regions with low moist static energy, yielding a positive feedback.}, author = {Muller, Caroline J and Held, Isaac M.}, issn = {0022-4928}, journal = {Journal of the Atmospheric Sciences}, keywords = {Atmospheric Science}, number = {8}, pages = {2551--2565}, publisher = {American Meteorological Society}, title = {{Detailed investigation of the self-aggregation of convection in cloud-resolving simulations}}, doi = {10.1175/jas-d-11-0257.1}, volume = {69}, year = {2012}, } @article{9451, abstract = {The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes DNA demethylation before fertilization, but the targeting preferences, mechanism, and biological significance of this process remain unclear. Here, we show that active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all of the demethylation in the central cell and preferentially targets small, AT-rich, and nucleosome-depleted euchromatic transposable elements. The vegetative cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation of similar sequences, and lack of DEMETER in vegetative cells causes reduced small RNA–directed DNA methylation of transposons in sperm. Our results demonstrate that demethylation in companion cells reinforces transposon methylation in plant gametes and likely contributes to stable silencing of transposable elements across generations.}, author = {Ibarra, Christian A. and Feng, Xiaoqi and Schoft, Vera K. and Hsieh, Tzung-Fu and Uzawa, Rie and Rodrigues, Jessica A. and Zemach, Assaf and Chumak, Nina and Machlicova, Adriana and Nishimura, Toshiro and Rojas, Denisse and Fischer, Robert L. and Tamaru, Hisashi and Zilberman, Daniel}, issn = {1095-9203}, journal = {Science}, number = {6100}, pages = {1360--1364}, publisher = {American Association for the Advancement of Science}, title = {{Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes}}, doi = {10.1126/science.1224839}, volume = {337}, year = {2012}, } @article{9535, abstract = {The most well-studied function of DNA methylation in eukaryotic cells is the transcriptional silencing of genes and transposons. More recent results showed that many eukaryotes methylate the bodies of genes as well and that this methylation correlates with transcriptional activity rather than repression. The purpose of gene body methylation remains mysterious, but is potentially related to the histone variant H2A.Z. Studies in plants and animals have shown that the genome-wide distributions of H2A.Z and DNA methylation are strikingly anticorrelated. Furthermore, we and other investigators have shown that this relationship is likely to be the result of an ancient but unknown mechanism by which DNA methylation prevents the incorporation of H2A.Z. Recently, we discovered strong correlations between the presence of H2A.Z within gene bodies, the degree to which a gene's expression varies across tissue types or environmental conditions, and transcriptional misregulation in an h2a.z mutant. We propose that one basal function of gene body methylation is the establishment of constitutive expression patterns within housekeeping genes by excluding H2A.Z from their bodies.}, author = {Coleman-Derr, D. and Zilberman, Daniel}, issn = {1943-4456}, journal = {Cold Spring Harbor Symposia on Quantitative Biology}, pages = {147--154}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{DNA methylation, H2A.Z, and the regulation of constitutive expression}}, doi = {10.1101/sqb.2012.77.014944}, volume = {77}, year = {2012}, } @article{3242, abstract = {Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).}, author = {Konrad, Matthias and Vyleta, Meghan and Theis, Fabian and Stock, Miriam and Tragust, Simon and Klatt, Martina and Drescher, Verena and Marr, Carsten and Ugelvig, Line V and Cremer, Sylvia}, journal = {PLoS Biology}, number = {4}, publisher = {Public Library of Science}, title = {{Social transfer of pathogenic fungus promotes active immunisation in ant colonies}}, doi = {10.1371/journal.pbio.1001300}, volume = {10}, year = {2012}, } @misc{9755, abstract = {Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).}, author = {Konrad, Matthias and Vyleta, Meghan and Theis, Fabian and Stock, Miriam and Klatt, Martina and Drescher, Verena and Marr, Carsten and Ugelvig, Line V and Cremer, Sylvia}, publisher = {Dryad}, title = {{Data from: Social transfer of pathogenic fungus promotes active immunisation in ant colonies}}, doi = {10.5061/dryad.sv37s}, year = {2012}, } @misc{9758, abstract = {We propose a two-step procedure for estimating multiple migration rates in an approximate Bayesian computation (ABC) framework, accounting for global nuisance parameters. The approach is not limited to migration, but generally of interest for inference problems with multiple parameters and a modular structure (e.g. independent sets of demes or loci). We condition on a known, but complex demographic model of a spatially subdivided population, motivated by the reintroduction of Alpine ibex (Capra ibex) into Switzerland. In the first step, the global parameters ancestral mutation rate and male mating skew have been estimated for the whole population in Aeschbacher et al. (Genetics 2012; 192: 1027). In the second step, we estimate in this study the migration rates independently for clusters of demes putatively connected by migration. For large clusters (many migration rates), ABC faces the problem of too many summary statistics. We therefore assess by simulation if estimation per pair of demes is a valid alternative. We find that the trade-off between reduced dimensionality for the pairwise estimation on the one hand and lower accuracy due to the assumption of pairwise independence on the other depends on the number of migration rates to be inferred: the accuracy of the pairwise approach increases with the number of parameters, relative to the joint estimation approach. To distinguish between low and zero migration, we perform ABC-type model comparison between a model with migration and one without. Applying the approach to microsatellite data from Alpine ibex, we find no evidence for substantial gene flow via migration, except for one pair of demes in one direction.}, author = {Aeschbacher, Simon and Futschik, Andreas and Beaumont, Mark}, publisher = {Dryad}, title = {{Data from: Approximate Bayesian computation for modular inference problems with many parameters: the example of migration rates}}, doi = {10.5061/dryad.274b1}, year = {2012}, } @misc{9757, abstract = {To fight infectious diseases, host immune defences are employed at multiple levels. Sanitary behaviour, such as pathogen avoidance and removal, acts as a first line of defence to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care towards pathogen-exposed group members [2]. One of the most common behaviours is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores as it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behaviour extends current understanding of grooming and the establishment of social immunity in insect societies.}, author = {Tragust, Simon and Mitteregger, Barbara and Barone, Vanessa and Konrad, Matthias and Ugelvig, Line V and Cremer, Sylvia}, publisher = {Dryad}, title = {{Data from: Ants disinfect fungus-exposed brood by oral uptake and spread of their poison}}, doi = {10.5061/dryad.61649}, year = {2012}, } @article{8504, abstract = {In this paper we present a surprising example of a Cr unimodal map of an interval f:I→I whose number of periodic points Pn(f)=∣{x∈I:fnx=x}∣ grows faster than any ahead given sequence along a subsequence nk=3k. This example also shows that ‘non-flatness’ of critical points is necessary for the Martens–de Melo–van Strien theorem [M. Martens, W. de Melo and S. van Strien. Julia–Fatou–Sullivan theory for real one-dimensional dynamics. Acta Math.168(3–4) (1992), 273–318] to hold.}, author = {Kaloshin, Vadim and KOZLOVSKI, O. S.}, issn = {0143-3857}, journal = {Ergodic Theory and Dynamical Systems}, keywords = {Applied Mathematics, General Mathematics}, number = {1}, pages = {159--165}, publisher = {Cambridge University Press}, title = {{A Cr unimodal map with an arbitrary fast growth of the number of periodic points}}, doi = {10.1017/s0143385710000817}, volume = {32}, year = {2012}, } @article{8503, abstract = {We prove there are finitely many isometry classes of planar central configurations (also called relative equilibria) in the Newtonian 5-body problem, except perhaps if the 5-tuple of positive masses belongs to a given codimension 2 subvariety of the mass space.}, author = {Albouy, Alain and Kaloshin, Vadim}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {1}, pages = {535--588}, publisher = {Princeton University Press}, title = {{Finiteness of central configurations of five bodies in the plane}}, doi = {10.4007/annals.2012.176.1.10}, volume = {176}, year = {2012}, } @article{887, abstract = {A subject of extensive study in evolutionary theory has been the issue of how neutral, redundant copies can be maintained in the genome for long periods of time. Concurrently, examples of adaptive gene duplications to various environmental conditions in different species have been described. At this point, it is too early to tell whether or not a substantial fraction of gene copies have initially achieved fixation by positive selection for increased dosage. Nevertheless, enough examples have accumulated in the literature that such a possibility should be considered. Here, I review the recent examples of adaptive gene duplications and make an attempt to draw generalizations on what types of genes may be particularly prone to be selected for under certain environmental conditions. The identification of copy-number variation in ecological field studies of species adapting to stressful or novel environmental conditions may improve our understanding of gene duplications as a mechanism of adaptation and its relevance to the long-term persistence of gene duplications.}, author = {Fyodor Kondrashov}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1749}, pages = {5048 -- 5057}, publisher = {Royal Society, The}, title = {{Gene duplication as a mechanism of genomic adaptation to a changing environment}}, doi = {10.1098/rspb.2012.1108}, volume = {279}, year = {2012}, } @article{9049, abstract = {Diffusiophoretic motion of colloids and macromolecules under salt gradients exhibits a logarithmic-sensing, i.e. the particle velocity is proportional to the spatial gradient of the logarithm of the salt concentration, as VDP = DDP∇logc. Here we explore experimentally the implications of this log-sensing behavior, on the basis of a hydrogel microfluidic device allowing to build spatially and temporally controlled gradients. We first demonstrate that the non-linearity of the salt-taxis leads to a trapping of particles under concentration gradient oscillations via a rectification of the motion. As an alternative, we make use of the high sensitivity of diffusiophoretic migration to vanishing salt concentration due to the log-sensing: in a counter-intuitive way, a vanishing gradient can lead to measurable velocity provided that the solute concentration is low enough, thus keeping ∇c/c finite. We show that this leads to a strong segregation of particles in osmotic shock configuration, resulting from a step change of the salt concentration at the boundaries. These various phenomena are rationalized on the basis of a theoretical description for the time-dependent Smoluchowski equation for the colloidal density.}, author = {Palacci, Jérémie A and Cottin-Bizonne, Cécile and Ybert, Christophe and Bocquet, Lydéric}, issn = {1744-6848}, journal = {Soft Matter}, number = {4}, pages = {980--994}, publisher = {Royal Society of Chemistry}, title = {{Osmotic traps for colloids and macromolecules based on logarithmic sensing in salt taxis}}, doi = {10.1039/c1sm06395b}, volume = {8}, year = {2012}, } @article{922, abstract = {We study theoretically the morphologies of biological tubes affected by various pathologies. When epithelial cells grow, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated: varicose, dilated, sinuous, or sausagelike. They are all found in pathologies of tracheal, renal tubes, or arteries. The final shape depends crucially on the mechanical parameters of the tissues: Young's modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.}, author = {Hannezo, Edouard B and Prost, Jacques and Joanny, Jean}, journal = {Physical Review Letters}, number = {1}, publisher = {American Physical Society}, title = {{Mechanical instabilities of biological tubes}}, doi = {10.1103/PhysRevLett.109.018101}, volume = {109}, year = {2012}, } @article{9499, abstract = {EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism.}, author = {Kim, Sang Yeol and Lee, Jungeun and Eshed-Williams, Leor and Zilberman, Daniel and Sung, Z. Renee}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {3}, publisher = {Public Library of Science}, title = {{EMF1 and PRC2 cooperate to repress key regulators of Arabidopsis development}}, doi = {10.1371/journal.pgen.1002512}, volume = {8}, year = {2012}, } @article{9497, abstract = {The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that loss of H2A.Z in Arabidopsis has only a minor effect on the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is primarily caused by the exclusion of H2A.Z from methylated DNA. RNA sequencing and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. Loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to environmental and developmental stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes.}, author = {Coleman-Derr, Devin and Zilberman, Daniel}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {10}, publisher = {Public Library of Science}, title = {{Deposition of histone variant H2A.Z within gene bodies regulates responsive genes}}, doi = {10.1371/journal.pgen.1002988}, volume = {8}, year = {2012}, } @article{9528, abstract = {Accumulating evidence points toward diverse functions for plant chromatin. Remarkable progress has been made over the last few years in elucidating the mechanisms for a number of these functions. Activity of the histone demethylase IBM1 accurately targets DNA methylation to silent repeats and transposable elements, not to genes. A genetic screen uncovered the surprising role of H2A.Z-containing nucleosomes in sensing precise differences in ambient temperature and consequent gene regulation. Precise maintenance of chromosome number is assured by a histone modification that suppresses inappropriate DNA replication and by centromeric histone H3 regulation of chromosome segregation. Histones and noncoding RNAs regulate FLOWERING LOCUS C, the expression of which quantitatively measures the duration of cold exposure, functioning as memory of winter. These findings are a testament to the power of using plants to research chromatin organization, and demonstrate examples of how chromatin functions to achieve biological accuracy, precision, and memory.}, author = {Huff, Jason T. and Zilberman, Daniel}, issn = {0959-437X}, journal = {Current Opinion in Genetics and Development}, number = {2}, pages = {132--138}, publisher = {Elsevier}, title = {{Regulation of biological accuracy, precision, and memory by plant chromatin organization}}, doi = {10.1016/j.gde.2012.01.007}, volume = {22}, year = {2012}, } @article{966, abstract = {Motivated by recent experiments on Ba3NiSb2O 9, we investigate possible quantum spin liquid ground states for spin S=1 Heisenberg models on the triangular lattice. We use variational Monte Carlo techniques to calculate the energies of microscopic spin liquid wave functions where spin is represented by three flavors of fermionic spinon operators. These energies are compared with the energies of various competing three-sublattice ordered states. Our approach shows that the antiferromagnetic Heisenberg model with biquadratic term and single-ion anisotropy does not have a low-temperature spin liquid phase. However, for an SU(3)-invariant model with sufficiently strong ring-exchange terms, we find a paired chiral quantum spin liquid with a Fermi surface of deconfined spinons that is stable against all types of ordering patterns we considered. We discuss the physics of this exotic spin liquid state in relation to the recent experiment and suggest new ways to test this scenario.}, author = {Bieri, Samuel and Maksym Serbyn and Senthil, Todadri S and Lee, Patrick}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {22}, publisher = {American Physical Society}, title = {{Paired chiral spin liquid with a Fermi surface in S=1 model on the triangular lattice}}, doi = {10.1103/PhysRevB.86.224409}, volume = {86}, year = {2012}, } @article{2968, abstract = {Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, Cecidostiba semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and-using triplet alignments of intronic loci-quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times. © 2012 Blackwell Publishing Ltd.}, author = {Lohse, Konrad and Barton, Nicholas H and Melika, George and Stone, Graham}, journal = {Molecular Ecology}, number = {18}, pages = {4605 -- 4617}, publisher = {Wiley-Blackwell}, title = {{A likelihood based comparison of population histories in a parasitoid guild}}, doi = {10.1111/j.1365-294X.2012.05700.x}, volume = {21}, year = {2012}, } @misc{13075, abstract = {Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, C. semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and - using triplet alignments of intronic loci - quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times.}, author = {Lohse, Konrad and Barton, Nicholas H and Stone, Graham and Melika, George}, publisher = {Dryad}, title = {{Data from: A likelihood-based comparison of population histories in a parasitoid guild}}, doi = {10.5061/DRYAD.0G0FS}, year = {2012}, } @article{13407, abstract = {We show that diamagnetic particles can be remotely manipulated by a magnet by the reversible adsorption of dual-responsive, light-switchable/superparamagnetic nanoparticles down to their surface. Adsorption occurs upon exposure to UV light, and can be reversed thermally or by ambient light. The dynamic self-assembly of thin films of the dual-responsive nanoparticles induces attractive interactions between diamagnetic particles. We demonstrate that catalytic amounts of the dual-responsive nanoparticles are sufficient to magnetically guide and deliver the diamagnetic particles to desired locations, where they can then be released by disassembling the dynamic layers of superparamagnetic nanoparticles with visible light.}, author = {Chovnik, Olga and Balgley, Renata and Goldman, Joel R. and Klajn, Rafal}, issn = {1520-5126}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {48}, pages = {19564--19567}, publisher = {American Chemical Society}, title = {{Dynamically self-assembling carriers enable guiding of diamagnetic particles by weak magnets}}, doi = {10.1021/ja309633v}, volume = {134}, year = {2012}, } @article{13408, abstract = {Well-defined metallic nanobowls can be prepared by extending the concept of a protecting group to colloidal synthesis. Magnetic nanoparticles are employed as “protecting groups” during the galvanic replacement of silver with gold. The replacement reaction is accompanied by spontantous dissociation of the protecting groups, leaving behind metallic nanobowls.}, author = {Ridelman, Yonatan and Singh, Gurvinder and Popovitz-Biro, Ronit and Wolf, Sharon G. and Das, Sanjib and Klajn, Rafal}, issn = {1613-6829}, journal = {Small}, keywords = {Biomaterials, Biotechnology, General Materials Science, General Chemistry}, number = {5}, pages = {654--660}, publisher = {Wiley}, title = {{Metallic nanobowls by galvanic replacement reaction on heterodimeric nanoparticles}}, doi = {10.1002/smll.201101882}, volume = {8}, year = {2012}, } @inproceedings{10903, abstract = {We propose a logic-based framework for automated reasoning about sequential programs manipulating singly-linked lists and arrays with unbounded data. We introduce the logic SLAD, which allows combining shape constraints, written in a fragment of Separation Logic, with data and size constraints. We address the problem of checking the entailment between SLAD formulas, which is crucial in performing pre-post condition reasoning. Although this problem is undecidable in general for SLAD, we propose a sound and powerful procedure that is able to solve this problem for a large class of formulas, beyond the capabilities of existing techniques and tools. We prove that this procedure is complete, i.e., it is actually a decision procedure for this problem, for an important fragment of SLAD including known decidable logics. We implemented this procedure and shown its preciseness and its efficiency on a significant benchmark of formulas.}, author = {Bouajjani, Ahmed and Dragoi, Cezara and Enea, Constantin and Sighireanu, Mihaela}, booktitle = {Automated Technology for Verification and Analysis}, isbn = {9783642333859}, issn = {1611-3349}, location = {Thiruvananthapuram, India}, pages = {167--182}, publisher = {Springer}, title = {{Accurate invariant checking for programs manipulating lists and arrays with infinite data}}, doi = {10.1007/978-3-642-33386-6_14}, volume = {7561}, year = {2012}, } @inproceedings{10905, abstract = {Energy games belong to a class of turn-based two-player infinite-duration games played on a weighted directed graph. It is one of the rare and intriguing combinatorial problems that lie in NP ∩ co−NP, but are not known to be in P. While the existence of polynomial-time algorithms has been a major open problem for decades, there is no algorithm that solves any non-trivial subclass in polynomial time. In this paper, we give several results based on the weight structures of the graph. First, we identify a notion of penalty and present a polynomial-time algorithm when the penalty is large. Our algorithm is the first polynomial-time algorithm on a large class of weighted graphs. It includes several counter examples that show that many previous algorithms, such as value iteration and random facet algorithms, require at least sub-exponential time. Our main technique is developing the first non-trivial approximation algorithm and showing how to convert it to an exact algorithm. Moreover, we show that in a practical case in verification where weights are clustered around a constant number of values, the energy game problem can be solved in polynomial time. We also show that the problem is still as hard as in general when the clique-width is bounded or the graph is strongly ergodic, suggesting that restricting graph structures need not help.}, author = {Chatterjee, Krishnendu and Henzinger, Monika H and Krinninger, Sebastian and Nanongkai, Danupon}, booktitle = {Algorithms – ESA 2012}, isbn = {9783642330896}, issn = {1611-3349}, location = {Ljubljana, Slovenia}, pages = {301--312}, publisher = {Springer}, title = {{Polynomial-time algorithms for energy games with special weight structures}}, doi = {10.1007/978-3-642-33090-2_27}, volume = {7501}, year = {2012}, } @inproceedings{10906, abstract = {HSF(C) is a tool that automates verification of safety and liveness properties for C programs. This paper describes the verification approach taken by HSF(C) and provides instructions on how to install and use the tool.}, author = {Grebenshchikov, Sergey and Gupta, Ashutosh and Lopes, Nuno P. and Popeea, Corneliu and Rybalchenko, Andrey}, booktitle = {Tools and Algorithms for the Construction and Analysis of Systems}, editor = {Flanagan, Cormac and König, Barbara}, isbn = {9783642287558}, issn = {1611-3349}, location = {Tallinn, Estonia}, pages = {549--551}, publisher = {Springer}, title = {{HSF(C): A software verifier based on Horn clauses}}, doi = {10.1007/978-3-642-28756-5_46}, volume = {7214}, year = {2012}, } @inbook{5745, author = {Gupta, Ashutosh}, booktitle = {Automated Technology for Verification and Analysis}, isbn = {9783642333859}, issn = {1611-3349}, location = {Thiruvananthapuram, Kerala, India}, pages = {107--121}, publisher = {Springer Berlin Heidelberg}, title = {{Improved Single Pass Algorithms for Resolution Proof Reduction}}, doi = {10.1007/978-3-642-33386-6_10}, volume = {7561}, year = {2012}, } @inproceedings{3251, abstract = {Many infinite state systems can be seen as well-structured transition systems (WSTS), i.e., systems equipped with a well-quasi-ordering on states that is also a simulation relation. WSTS are an attractive target for formal analysis because there exist generic algorithms that decide interesting verification problems for this class. Among the most popular algorithms are acceleration-based forward analyses for computing the covering set. Termination of these algorithms can only be guaranteed for flattable WSTS. Yet, many WSTS of practical interest are not flattable and the question whether any given WSTS is flattable is itself undecidable. We therefore propose an analysis that computes the covering set and captures the essence of acceleration-based algorithms, but sacrifices precision for guaranteed termination. Our analysis is an abstract interpretation whose abstract domain builds on the ideal completion of the well-quasi-ordered state space, and a widening operator that mimics acceleration and controls the loss of precision of the analysis. We present instances of our framework for various classes of WSTS. Our experience with a prototype implementation indicates that, despite the inherent precision loss, our analysis often computes the precise covering set of the analyzed system.}, author = {Zufferey, Damien and Wies, Thomas and Henzinger, Thomas A}, location = {Philadelphia, PA, USA}, pages = {445 -- 460}, publisher = {Springer}, title = {{Ideal abstractions for well structured transition systems}}, doi = {10.1007/978-3-642-27940-9_29}, volume = {7148}, year = {2012}, } @article{3157, abstract = {Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.}, author = {Diaz Jr, Luis and Williams, Richard and Wu, Jian and Kinde, Isaac and Hecht, Joel and Berlin, Jordan and Allen, Benjamin and Božić, Ivana and Reiter, Johannes and Nowak, Martin and Kinzler, Kenneth and Oliner, Kelly and Vogelstein, Bert}, journal = {Nature}, number = {7404}, pages = {537 -- 540}, publisher = {Nature Publishing Group}, title = {{The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers}}, doi = {10.1038/nature11219}, volume = {486}, year = {2012}, } @article{3260, abstract = {Many scenarios in the living world, where individual organisms compete for winning positions (or resources), have properties of auctions. Here we study the evolution of bids in biological auctions. For each auction, n individuals are drawn at random from a population of size N. Each individual makes a bid which entails a cost. The winner obtains a benefit of a certain value. Costs and benefits are translated into reproductive success (fitness). Therefore, successful bidding strategies spread in the population. We compare two types of auctions. In “biological all-pay auctions”, the costs are the bid for every participating individual. In “biological second price all-pay auctions”, the cost for everyone other than the winner is the bid, but the cost for the winner is the second highest bid. Second price all-pay auctions are generalizations of the “war of attrition” introduced by Maynard Smith. We study evolutionary dynamics in both types of auctions. We calculate pairwise invasion plots and evolutionarily stable distributions over the continuous strategy space. We find that the average bid in second price all-pay auctions is higher than in all-pay auctions, but the average cost for the winner is similar in both auctions. In both cases, the average bid is a declining function of the number of participants, n. The more individuals participate in an auction the smaller is the chance of winning, and thus expensive bids must be avoided. }, author = {Chatterjee, Krishnendu and Reiter, Johannes and Nowak, Martin}, journal = {Theoretical Population Biology}, number = {1}, pages = {69 -- 80}, publisher = {Academic Press}, title = {{Evolutionary dynamics of biological auctions}}, doi = {10.1016/j.tpb.2011.11.003}, volume = {81}, year = {2012}, } @article{3258, abstract = {CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.}, author = {Kim, Sooyun and Guzmán, José and Hu, Hua and Jonas, Peter M}, issn = {1546-1726}, journal = {Nature Neuroscience}, number = {4}, pages = {600 -- 606}, publisher = {Nature Publishing Group}, title = {{Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons}}, doi = {10.1038/nn.3060}, volume = {15}, year = {2012}, } @phdthesis{2964, abstract = {CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. These neurons receive multiple excitatory inputs from numerous sources. Therefore, the rules of spatiotemporal integration of multiple synaptic inputs and propagation of action potentials are important to understand how CA3 neurons contribute to higher brain functions at cellular level. By using confocally targeted patch-clamp recording techniques, we investigated the biophysical properties of rat CA3 pyramidal neuron dendrites. We found two distinct dendritic domains critical for action potential initiation and propagation: In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+-channel mediated dendritic spikes are efficiently evoked by local dendritic depolarization or waveforms mimicking synaptic events. These findings can be explained by a high Na+-to-K+ conductance density ratio of CA3 pyramidal neuron dendrites. The results challenge the prevailing view that proximal mossy fiber inputs activate CA3 pyramidal neurons more efficiently than distal perforant inputs by showing that the distal synapses trigger a different form of activity represented by dendritic spikes. The high probability of dendritic spike initiation in the distal area may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. }, author = {Kim, Sooyun}, issn = {2663-337X}, pages = {65}, publisher = {Institute of Science and Technology Austria}, title = {{Active properties of hippocampal CA3 pyramidal neuron dendrites}}, year = {2012}, } @article{3246, abstract = {Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis.}, author = {Barone, Vanessa and Heisenberg, Carl-Philipp J}, journal = {Current Opinion in Cell Biology}, number = {1}, pages = {148 -- 153}, publisher = {Elsevier}, title = {{Cell adhesion in embryo morphogenesis}}, doi = {10.1016/j.ceb.2011.11.006}, volume = {24}, year = {2012}, } @article{12198, abstract = {The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes DNA demethylation before fertilization, but the targeting preferences, mechanism, and biological significance of this process remain unclear. Here, we show that active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all of the demethylation in the central cell and preferentially targets small, AT-rich, and nucleosome-depleted euchromatic transposable elements. The vegetative cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation of similar sequences, and lack of DEMETER in vegetative cells causes reduced small RNA–directed DNA methylation of transposons in sperm. Our results demonstrate that demethylation in companion cells reinforces transposon methylation in plant gametes and likely contributes to stable silencing of transposable elements across generations.}, author = {Ibarra, Christian A. and Feng, Xiaoqi and Schoft, Vera K. and Hsieh, Tzung-Fu and Uzawa, Rie and Rodrigues, Jessica A. and Zemach, Assaf and Chumak, Nina and Machlicova, Adriana and Nishimura, Toshiro and Rojas, Denisse and Fischer, Robert L. and Tamaru, Hisashi and Zilberman, Daniel}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {6100}, pages = {1360--1364}, publisher = {American Association for the Advancement of Science}, title = {{Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes}}, doi = {10.1126/science.1224839}, volume = {337}, year = {2012}, } @article{6588, abstract = {First we note that the best polynomial approximation to vertical bar x vertical bar on the set, which consists of an interval on the positive half-axis and a point on the negative half-axis, can be given by means of the classical Chebyshev polynomials. Then we explore the cases when a solution of the related problem on two intervals can be given in elementary functions.}, author = {Pausinger, Florian}, issn = {1812-9471}, journal = {Journal of Mathematical Physics, Analysis, Geometry}, number = {1}, pages = {63--78}, publisher = {B. Verkin Institute for Low Temperature Physics and Engineering}, title = {{Elementary solutions of the Bernstein problem on two intervals}}, volume = {8}, year = {2012}, } @inproceedings{3123, abstract = {We introduce the idea of using an explicit triangle mesh to track the air/fluid interface in a smoothed particle hydrodynamics (SPH) simulator. Once an initial surface mesh is created, this mesh is carried forward in time using nearby particle velocities to advect the mesh vertices. The mesh connectivity remains mostly unchanged across time-steps; it is only modified locally for topology change events or for the improvement of triangle quality. In order to ensure that the surface mesh does not diverge from the underlying particle simulation, we periodically project the mesh surface onto an implicit surface defined by the physics simulation. The mesh surface gives us several advantages over previous SPH surface tracking techniques. We demonstrate a new method for surface tension calculations that clearly outperforms the state of the art in SPH surface tension for computer graphics. We also demonstrate a method for tracking detailed surface information (like colors) that is less susceptible to numerical diffusion than competing techniques. Finally, our temporally-coherent surface mesh allows us to simulate high-resolution surface wave dynamics without being limited by the particle resolution of the SPH simulation.}, author = {Yu, Jihun and Wojtan, Christopher J and Turk, Greg and Yap, Chee}, booktitle = {Computer Graphics Forum}, issn = {1467-8659}, location = {Cagliari, Sardinia, Italy}, number = {2}, pages = {815 -- 824}, publisher = {Wiley}, title = {{Explicit mesh surfaces for particle based fluids}}, doi = {10.1111/j.1467-8659.2012.03062.x}, volume = {31}, year = {2012}, } @article{3244, abstract = {Bibliothekare haben die Aufgabe, sich mit neuen Medienformen auseinanderzusetzen. }, author = {Danowski, Patrick}, issn = {1869 -1137}, journal = {BuB - Forum Bibliothek und Information}, number = {4}, pages = {284}, publisher = {Fachzeitschrift des BIB – Berufsverband Information Bibliothek}, title = {{Die Zeit des Abwartens ist vorbei!}}, volume = {64}, year = {2012}, } @article{3243, abstract = {Wie wandelt sich das Berufsbild in Wissenschaftlichen Bibliotheken? Patrick Danowski gibt seine Einschätzung ab. }, author = {Danowski, Patrick}, issn = {1607-7172}, journal = {Büchereiperspektiven}, number = {1}, pages = {11}, publisher = {Büchereiverband Österreichs}, title = {{Zwischen Technologie und Information}}, volume = {2012}, year = {2012}, } @inproceedings{2915, author = {Kroemer, Oliver and Lampert, Christoph and Peters, Jan}, publisher = {Deutsches Zentrum für Luft und Raumfahrt}, title = {{Multi-modal learning for dynamic tactile sensing}}, year = {2012}, } @article{2912, author = {Edelsbrunner, Herbert and Strelkova, Nataliya}, journal = {Russian Mathematical Surveys}, number = {6}, pages = {1167–1168}, publisher = {Russian Academy of Sciences}, title = {{On the configuration space for the shortest networks}}, doi = {10.4213/rm9503}, volume = {67}, year = {2012}, } @inproceedings{3127, abstract = {When searching for characteristic subpatterns in potentially noisy graph data, it appears self-evident that having multiple observations would be better than having just one. However, it turns out that the inconsistencies introduced when different graph instances have different edge sets pose a serious challenge. In this work we address this challenge for the problem of finding maximum weighted cliques. We introduce the concept of most persistent soft-clique. This is subset of vertices, that 1) is almost fully or at least densely connected, 2) occurs in all or almost all graph instances, and 3) has the maximum weight. We present a measure of clique-ness, that essentially counts the number of edge missing to make a subset of vertices into a clique. With this measure, we show that the problem of finding the most persistent soft-clique problem can be cast either as: a) a max-min two person game optimization problem, or b) a min-min soft margin optimization problem. Both formulations lead to the same solution when using a partial Lagrangian method to solve the optimization problems. By experiments on synthetic data and on real social network data, we show that the proposed method is able to reliably find soft cliques in graph data, even if that is distorted by random noise or unreliable observations.}, author = {Quadrianto, Novi and Lampert, Christoph and Chen, Chao}, booktitle = {Proceedings of the 29th International Conference on Machine Learning}, location = {Edinburgh, United Kingdom}, pages = {211--218}, publisher = {ML Research Press}, title = {{The most persistent soft-clique in a set of sampled graphs}}, year = {2012}, }