@article{8022, abstract = {Populations of neurons in motor cortex engage in complex transient dynamics of large amplitude during the execution of limb movements. Traditional network models with stochastically assigned synapses cannot reproduce this behavior. Here we introduce a class of cortical architectures with strong and random excitatory recurrence that is stabilized by intricate, fine-tuned inhibition, optimized from a control theory perspective. Such networks transiently amplify specific activity states and can be used to reliably execute multidimensional movement patterns. Similar to the experimental observations, these transients must be preceded by a steady-state initialization phase from which the network relaxes back into the background state by way of complex internal dynamics. In our networks, excitation and inhibition are as tightly balanced as recently reported in experiments across several brain areas, suggesting inhibitory control of complex excitatory recurrence as a generic organizational principle in cortex.}, author = {Hennequin, Guillaume and Vogels, Tim P and Gerstner, Wulfram}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1394--1406}, publisher = {Elsevier}, title = {{Optimal control of transient dynamics in balanced networks supports generation of complex movements}}, doi = {10.1016/j.neuron.2014.04.045}, volume = {82}, year = {2014}, } @article{809, abstract = {The assembly of HIV-1 is mediated by oligomerization of the major structural polyprotein, Gag, into a hexameric protein lattice at the plasma membrane of the infected cell. This leads to budding and release of progeny immature virus particles. Subsequent proteolytic cleavage of Gag triggers rearrangement of the particles to form mature infectious virions. Obtaining a structural model of the assembled lattice of Gag within immature virus particles is necessary to understand the interactions that mediate assembly of HIV-1 particles in the infected cell, and to describe the substrate that is subsequently cleaved by the viral protease. An 8-Å resolution structure of an immature virus-like tubular array assembled from a Gag-derived protein of the related retrovirus Mason-Pfizer monkey virus (M-PMV) has previously been reported, and a model for the arrangement of the HIV-1 capsid (CA) domains has been generated based on homology to this structure. Here we have assembled tubular arrays of a HIV-1 Gag-derived protein with an immature-like arrangement of the C-terminal CA domains and have solved their structure by using hybrid cryo-EM and tomography analysis. The structure reveals the arrangement of the C-terminal domain of CA within an immature-like HIV-1 Gag lattice, and provides, to our knowledge, the first high-resolution view of the region immediately downstream of CA, which is essential for assembly, and is significantly different from the respective region in M-PMV. Our results reveal a hollow column of density for this region in HIV-1 that is compatible with the presence of a six-helix bundle at this position.}, author = {Bharata, Tanmay A and Menendez, Luis R and Hagena, Wim J and Luxd, Vanda and Igonete, Sebastien and Schorba, Martin and Florian Schur and Kraüsslich, Hans Georg and Briggsa, John A}, journal = {PNAS}, number = {22}, pages = {8233 -- 8238}, publisher = {National Academy of Sciences}, title = {{Cryo electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly}}, doi = {10.1073/pnas.1401455111}, volume = {111}, year = {2014}, } @article{8244, abstract = {Passive immunotherapy with monoclonal antibodies represents a cornerstone of human anticancer therapies, but has not been established in veterinary medicine yet. As the tumor-associated antigen EGFR (ErbB-1) is highly conserved between humans and dogs, and considering the effectiveness of the anti-EGFR antibody cetuximab in human clinical oncology, we present here a “caninized” version of this antibody, can225IgG, for comparative oncology studies. Variable region genes of 225, the murine precursor of cetuximab, were fused with canine constant heavy gamma and kappa chain genes, respectively, and transfected into Chinese hamster ovary (CHO) DUKX-B11 cells. Of note, 480 clones were screened and the best clones were selected according to productivity and highest specificity in EGFR-coated ELISA. Upon purification with Protein G, the recombinant cetuximab-like canine IgG was tested for integrity, correct assembly, and functionality. Specific binding to the surface of EGFR-overexpressing cells was assessed by flow cytometry and immunofluorescence; moreover, binding to canine mammary tissue was demonstrated by immunohistochemistry. In cell viability and proliferation assays, incubation with can225IgG led to significant tumor cell growth inhibition. Moreover, this antibody mediated significant tumor cell killing via phagocytosis in vitro. We thus present here, for the first time, the generation of a canine IgG antibody and its hypothetical structure. On the basis of its cetuximab-like binding site, on the one hand, and the expression of a 91% homologous EGFR molecule in canine cancer, on the other hand, this antibody may be a promising research compound to establish passive immunotherapy in dog patients with cancer.}, author = {Singer, J. and Fazekas, Judit and Wang, W. and Weichselbaumer, M. and Matz, M. and Mader, A. and Steinfellner, W. and Meitz, S. and Mechtcheriakova, D. and Sobanov, Y. and Willmann, M. and Stockner, T. and Spillner, E. and Kunert, R. and Jensen-Jarolim, E.}, issn = {1535-7163}, journal = {Molecular Cancer Therapeutics}, number = {7}, pages = {1777--1790}, publisher = {American Association for Cancer Research}, title = {{Generation of a canine anti-EGFR (ErbB-1) antibody for passive immunotherapy in dog cancer patients}}, doi = {10.1158/1535-7163.mct-13-0288}, volume = {13}, year = {2014}, } @article{8459, abstract = {Nuclear magnetic resonance (NMR) is a powerful tool for observing the motion of biomolecules at the atomic level. One technique, the analysis of relaxation dispersion phenomenon, is highly suited for studying the kinetics and thermodynamics of biological processes. Built on top of the relax computational environment for NMR dynamics is a new dispersion analysis designed to be comprehensive, accurate and easy-to-use. The software supports more models, both numeric and analytic, than current solutions. An automated protocol, available for scripting and driving the graphical user interface (GUI), is designed to simplify the analysis of dispersion data for NMR spectroscopists. Decreases in optimization time are granted by parallelization for running on computer clusters and by skipping an initial grid search by using parameters from one solution as the starting point for another —using analytic model results for the numeric models, taking advantage of model nesting, and using averaged non-clustered results for the clustered analysis.}, author = {Morin, Sébastien and Linnet, Troels E and Lescanne, Mathilde and Schanda, Paul and Thompson, Gary S and Tollinger, Martin and Teilum, Kaare and Gagné, Stéphane and Marion, Dominique and Griesinger, Christian and Blackledge, Martin and d’Auvergne, Edward J}, issn = {1367-4803}, journal = {Bioinformatics}, keywords = {Statistics and Probability, Computational Theory and Mathematics, Biochemistry, Molecular Biology, Computational Mathematics, Computer Science Applications}, number = {15}, pages = {2219--2220}, publisher = {Oxford University Press}, title = {{Relax: The analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data}}, doi = {10.1093/bioinformatics/btu166}, volume = {30}, year = {2014}, } @article{8458, abstract = {The maintenance of bacterial cell shape and integrity is largely attributed to peptidoglycan, a highly cross-linked biopolymer. The transpeptidases that perform this cross-linking are important targets for antibiotics. Despite this biomedical importance, to date no structure of a protein in complex with an intact bacterial peptidoglycan has been resolved, primarily due to the large size and flexibility of peptidoglycan sacculi. Here we use solid-state NMR spectroscopy to derive for the first time an atomic model of an l,d-transpeptidase from Bacillus subtilis bound to its natural substrate, the intact B. subtilis peptidoglycan. Importantly, the model obtained from protein chemical shift perturbation data shows that both domains—the catalytic domain as well as the proposed peptidoglycan recognition domain—are important for the interaction and reveals a novel binding motif that involves residues outside of the classical enzymatic pocket. Experiments on mutants and truncated protein constructs independently confirm the binding site and the implication of both domains. Through measurements of dipolar-coupling derived order parameters of bond motion we show that protein binding reduces the flexibility of peptidoglycan. This first report of an atomic model of a protein–peptidoglycan complex paves the way for the design of new antibiotic drugs targeting l,d-transpeptidases. The strategy developed here can be extended to the study of a large variety of enzymes involved in peptidoglycan morphogenesis.}, author = {Schanda, Paul and Triboulet, Sébastien and Laguri, Cédric and Bougault, Catherine M. and Ayala, Isabel and Callon, Morgane and Arthur, Michel and Simorre, Jean-Pierre}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {51}, pages = {17852--17860}, publisher = {American Chemical Society}, title = {{Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan}}, doi = {10.1021/ja5105987}, volume = {136}, year = {2014}, } @article{8460, abstract = {The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states.}, author = {Ma, Peixiang and Haller, Jens D. and Zajakala, Jérémy and Macek, Pavel and Sivertsen, Astrid C. and Willbold, Dieter and Boisbouvier, Jérôme and Schanda, Paul}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {17}, pages = {4312--4317}, publisher = {Wiley}, title = {{Probing transient conformational states of proteins by solid-state R1ρ relaxation-dispersion NMR spectroscopy}}, doi = {10.1002/anie.201311275}, volume = {53}, year = {2014}, } @article{8501, abstract = {In this paper, we study small perturbations of a class of non-convex integrable Hamiltonians with two degrees of freedom, and we prove a result of diffusion for an open and dense set of perturbations, with an optimal time of diffusion which grows linearly with respect to the inverse of the size of the perturbation.}, author = {Bounemoura, Abed and Kaloshin, Vadim}, issn = {1609-3321}, journal = {Moscow Mathematical Journal}, keywords = {General Mathematics}, number = {2}, pages = {181--203}, publisher = {Independent University of Moscow}, title = {{Generic fast diffusion for a class of non-convex Hamiltonians with two degrees of freedom}}, doi = {10.17323/1609-4514-2014-14-2-181-203}, volume = {14}, year = {2014}, } @article{8500, abstract = {The main model studied in this paper is a lattice of pendula with a nearest‐neighbor coupling. If the coupling is weak, then the system is near‐integrable and KAM tori fill most of the phase space. For all KAM trajectories the energy of each pendulum stays within a narrow band for all time. Still, we show that for an arbitrarily weak coupling of a certain localized type, the neighboring pendula can exchange energy. In fact, the energy can be transferred between the pendula in any prescribed way.}, author = {Kaloshin, Vadim and Levi, Mark and Saprykina, Maria}, issn = {0010-3640}, journal = {Communications on Pure and Applied Mathematics}, keywords = {Applied Mathematics, General Mathematics}, number = {5}, pages = {748--775}, publisher = {Wiley}, title = {{Arnol′d diffusion in a pendulum lattice}}, doi = {10.1002/cpa.21509}, volume = {67}, year = {2014}, } @article{852, abstract = {Rapid divergence of gene copies after duplication is thought to determine the fate of the copies and evolution of novel protein functions. However, data on howlong the gene copies continue to experience an elevated rate of evolution remain scarce. Standard theory of gene duplications based on some level of genetic redundancy of gene copies predicts that the period of accelerated evolutionmust end relatively quickly. Using a maximum-likelihood approach we estimate preduplication, initial postduplication, and recent postduplication rates of evolution that occurred in themammalian lineage.Wefind that both gene copies experience a similar in magnitude acceleration in their rate of evolution. The copy located in the original genomic position typically returns to the preduplication rates of evolution in a short period of time. The burst of faster evolution of the copy that is located in a new genomic position typically lasts longer. Furthermore, the fast-evolving copies on average continue to evolve faster than the preduplication rates far longer than predicted by standard theory of gene duplications.We hypothesize that the prolonged elevated rates of evolution are determined by functional properties that were acquired during, or soon after, the gene duplication event. }, author = {Rosello, Oriol P and Fyodor Kondrashov}, journal = {Genome Biology and Evolution}, number = {8}, pages = {1949 -- 1955}, publisher = {Oxford University Press}, title = {{Long-Term asymmetrical acceleration of protein evolution after gene duplication}}, doi = {10.1093/gbe/evu159}, volume = {6}, year = {2014}, } @article{856, abstract = {The emergence of new genes throughout evolution requires rewiring and extension of regulatory networks. However, the molecular details of how the transcriptional regulation of new gene copies evolves remain largely unexplored. Here we show how duplication of a transcription factor gene allowed the emergence of two independent regulatory circuits. Interestingly, the ancestral transcription factor was promiscuous and could bind different motifs in its target promoters. After duplication, one paralogue evolved increased binding specificity so that it only binds one type of motif, whereas the other copy evolved a decreased activity so that it only activates promoters that contain multiple binding sites. Interestingly, only a few mutations in both the DNA-binding domains and in the promoter binding sites were required to gradually disentangle the two networks. These results reveal how duplication of a promiscuous transcription factor followed by concerted cis and trans mutations allows expansion of a regulatory network.}, author = {Pougach, Ksenia S and Voet, Arnout R and Fyodor Kondrashov and Voordeckers, Karin and Christiaens, Joaquin F and Baying, Bianka and Bénès, Vladimı́r and Sakai, Ryo and Aerts, Jan A and Zhu, Bo and Van Dijck, Patrick and Verstrepen, Kevin J}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network}}, doi = {10.1038/ncomms5868}, volume = {5}, year = {2014}, } @article{863, abstract = {The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes, and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well recognized in ctenophores, many bilaterian neuron-specific genes and genes of 'classical' neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.}, author = {Moroz, Leonid L and Kocot, Kevin M and Citarella, Mathew R and Dosung, Sohn and Norekian, Tigran P and Povolotskaya, Inna and Grigorenko, Anastasia P and Dailey, Christopher A and Berezikov, Eugene and Buckley, Katherine M and Ptitsyn, Andrey A and Reshetov, Denis A and Mukherjee, Krishanu and Moroz, Tatiana P and Bobkova, Yelena V and Yu, Fahong and Kapitonov, Vladimir V and Jurka, Jerzy W and Bobkov, Yuriy V and Swore, Joshua J and Girardo, David O and Fodor, Alexander and Gusev, Fedor E and Sanford, Rachel S and Bruders, Rebecca and Kittler, Ellen L and Mills, Claudia E and Rast, Jonathan P and Derelle, Romain and Solovyev, Victor and Fyodor Kondrashov and Swalla, Billie J and Sweedler, Jonathan V and Rogaev, Evgeny I and Halanych, Kenneth M and Kohn, Andrea B}, journal = {Nature}, number = {7503}, pages = {109 -- 114}, publisher = {Nature Publishing Group}, title = {{The ctenophore genome and the evolutionary origins of neural systems}}, doi = {10.1038/nature13400}, volume = {510}, year = {2014}, } @article{865, abstract = {Research on existing drugs often discovers novel mechanisms of their action and leads to the expansion of their therapeutic scope and subsequent remarketing. The Wnt signaling pathway is of the immediate therapeutic relevance, as it plays critical roles in cancer development and progression. However, drugs which disrupt this pathway are unavailable despite the high demand. Here we report an attempt to identify antagonists of the Wnt-FZD interaction among the library of the FDA-approved drugs. We performed an in silico screening which brought up several potential antagonists of the ligand-receptor interaction. 14 of these substances were tested using the TopFlash luciferase reporter assay and four of them identified as active and specific inhibitors of the Wnt3a-induced signaling. However, further analysis through GTP-binding and β-catenin stabilization assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the signaling at downstream levels. We further describe the previously unknown inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and provide data demonstrating its efficiency in suppressing growth of Wnt-dependent triple-negative breast cancer cells. These data provide a basis for further investigations of the efficiency of clofazimine in treatment of Wnt-dependent cancers.}, author = {Koval, Alexey V and Vlasov, Peter K and Shichkova, Polina and Khunderyakova, S and Markov, Yury and Panchenko, J and Volodina, A and Fyodor Kondrashov and Katanaev, Vladimir L}, journal = {Biochemical Pharmacology}, number = {4}, pages = {571 -- 578}, publisher = {Elsevier}, title = {{Anti leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling}}, doi = {10.1016/j.bcp.2013.12.007}, volume = {87}, year = {2014}, } @article{925, abstract = {The morphological stability of biological tubes is crucial for the efficient circulation of fluids and gases. Failure of this stability causes irregularly shaped tubes found in multiple pathological conditions. Here, we report that Drosophila mutants of the ESCRT III component Shrub/Vps32 exhibit a strikingly elongated sinusoidal tube phenotype. This is caused by excessive apical membrane synthesis accompanied by the ectopic accumulation and overactivation of Crumbs in swollen endosomes. Furthermore, we demonstrate that the apical extracellular matrix (aECM) of the tracheal tube is a viscoelastic material coupled with the apical membrane. We present a simple mechanical model in which aECM elasticity, apical membrane growth, and their interaction are three vital parameters determining the stability of biological tubes. Our findings demonstrate a mechanical role for the extracellular matrix and suggest that the interaction of the apical membrane and an elastic aECM determines the final morphology of biological tubes independent of cell shape.}, author = {Dong, Bo and Hannezo, Edouard B and Hayashi, Shigeo}, journal = {Cell Reports}, number = {4}, pages = {941 -- 950}, publisher = {Cell Press}, title = {{Balance between apical membrane growth and luminal matrix resistance determines epithelial tubule shape}}, doi = {10.1016/j.celrep.2014.03.066}, volume = {7}, year = {2014}, } @article{927, abstract = {Morphogenesis during embryo development requires the coordination of mechanical forces to generate the macroscopic shapes of organs. We propose a minimal theoretical model, based on cell adhesion and actomyosin contractility, which describes the various shapes of epithelial cells and the bending and buckling of epithelial sheets, as well as the relative stability of cellular tubes and spheres. We show that, to understand these processes, a full 3D description of the cells is needed, but that simple scaling laws can still be derived. The morphologies observed in vivo can be understood as stable points of mechanical equations and the transitions between them are either continuous or discontinuous. We then focus on epithelial sheet bending, a ubiquitous morphogenetic process. We calculate the curvature of an epithelium as a function of actin belt tension as well as of cell-cell and and cell-substrate tension. The model allows for a comparison of the relative stabilities of spherical or cylindrical cellular structures (acini or tubes). Finally, we propose a unique type of buckling instability of epithelia, driven by a flattening of individual cell shapes, and discuss experimental tests to verify our predictions.}, author = {Hannezo, Edouard B and Prost, Jacques and Joanny, Jean}, journal = {PNAS}, number = {1}, pages = {27 -- 32}, publisher = {National Academy of Sciences}, title = {{Theory of epithelial sheet morphology in three dimensions}}, doi = {10.1073/pnas.1312076111}, volume = {111}, year = {2014}, } @article{9519, abstract = {Transposons are selfish genetic sequences that can increase their copy number and inflict substantial damage on their hosts. To combat these genomic parasites, plants have evolved multiple pathways to identify and silence transposons by methylating their DNA. Plants have also evolved mechanisms to limit the collateral damage from the antitransposon machinery. In this review, we examine recent developments that have elucidated many of the molecular workings of these pathways. We also highlight the evidence that the methylation and demethylation pathways interact, indicating that plants have a highly sophisticated, integrated system of transposon defense that has an important role in the regulation of gene expression.}, author = {Kim, M. Yvonne and Zilberman, Daniel}, issn = {1878-4372}, journal = {Trends in Plant Science}, number = {5}, pages = {320--326}, publisher = {Elsevier}, title = {{DNA methylation as a system of plant genomic immunity}}, doi = {10.1016/j.tplants.2014.01.014}, volume = {19}, year = {2014}, } @article{96, abstract = {Multielectron spin qubits are demonstrated, and performance examined by comparing coherent exchange oscillations in coupled single-electron and multielectron quantum dots, measured in the same device. Fast (>1 GHz) exchange oscillations with a quality factor Q∼15 are found for the multielectron case, compared to Q∼2 for the single-electron case, the latter consistent with experiments in the literature. A model of dephasing that includes voltage and hyperfine noise is developed that is in good agreement with both single- and multielectron data, though in both cases additional exchange-independent dephasing is needed to obtain quantitative agreement across a broad parameter range.}, author = {Higginbotham, Andrew P and Kuemmeth, Ferdinand and Hanson, Micah and Gossard, Arthur and Marcus, Charles}, journal = {APS Physics, Physical Review Letters}, number = {2}, publisher = {American Physiological Society}, title = {{Coherent operations and screening in multielectron spin qubits}}, doi = {10.1103/PhysRevLett.112.026801}, volume = {112}, year = {2014}, } @article{9594, abstract = {Let d≥3 be a fixed integer. We give an asympotic formula for the expected number of spanning trees in a uniformly random d-regular graph with n vertices. (The asymptotics are as n→∞, restricted to even n if d is odd.) We also obtain the asymptotic distribution of the number of spanning trees in a uniformly random cubic graph, and conjecture that the corresponding result holds for arbitrary (fixed) d. Numerical evidence is presented which supports our conjecture.}, author = {Greenhill, Catherine and Kwan, Matthew Alan and Wind, David}, issn = {1077-8926}, journal = {The Electronic Journal of Combinatorics}, number = {1}, publisher = {The Electronic Journal of Combinatorics}, title = {{On the number of spanning trees in random regular graphs}}, doi = {10.37236/3752}, volume = {21}, year = {2014}, } @article{9655, abstract = {Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x–y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.}, author = {Perkovic, Mario and Kunz, Michael and Endesfelder, Ulrike and Bunse, Stefanie and Wigge, Christoph and Yu, Zhou and Hodirnau, Victor-Valentin and Scheffer, Margot P. and Seybert, Anja and Malkusch, Sebastian and Schuman, Erin M. and Heilemann, Mike and Frangakis, Achilleas S.}, issn = {1047-8477}, journal = {Journal of Structural Biology}, number = {2}, pages = {205--213}, publisher = {Elsevier}, title = {{Correlative light- and electron microscopy with chemical tags}}, doi = {10.1016/j.jsb.2014.03.018}, volume = {186}, year = {2014}, } @article{9686, abstract = {It is well known that ultrasonic vibration can soften metals, and this phenomenon has been widely exploited in industrial applications concerning metal forming and bonding. Recent experiments show that the simultaneous application of oscillatory stresses from audible to ultrasonic frequency ranges can lead to not only softening but also significant dislocation annihilation and subgrain formation in metal samples from the nano- to macro-size range. These findings indicate that the existing understanding of ultrasound softening – that the vibrations either impose additional stress waves to augment the quasi-static applied load, or cause heating of the metal, whereas the metal’s intrinsic deformation resistance or mechanism remains unaltered – is far from complete. To understand the softening and the associated enhanced subgrain formation and dislocation annihilation, a new simulator based on the dynamics of dislocation-density functions is employed. This new simulator considers the flux, production and annihilation, as well as the Taylor and elastic interactions between dislocation densities. Softening during vibrations as well as enhanced cell formation is predicted. The simulations reveal the main mechanism for subcell formation under oscillatory loadings to be the enhanced elimination of statistically stored dislocations (SSDs) by the oscillatory stress, leaving behind geometrically necessary dislocations with low Schmid factors which then form the subgrain walls. The oscillatory stress helps the depletion of the SSDs, because the chance for them to meet up and annihilate is increased with reversals of dislocation motions. This is the first simulation effort to successfully predict the cell formation phenomenon under vibratory loadings.}, author = {Cheng, Bingqing and Leung, H.S. and Ngan, A.H.W.}, issn = {1478-6443}, journal = {Philosophical Magazine}, number = {16-18}, pages = {1845--1865}, publisher = {Taylor & Francis}, title = {{Strength of metals under vibrations – dislocation-density-function dynamics simulations}}, doi = {10.1080/14786435.2014.897008}, volume = {95}, year = {2014}, } @article{2083, abstract = {Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.}, author = {Lagator, Mato and Morgan, Andrew and Neve, Paul and Colegrave, Nick}, journal = {Evolution}, number = {8}, pages = {2296 -- 2305}, publisher = {Wiley}, title = {{Role of sex and migration in adaptation to sink environments}}, doi = {10.1111/evo.12440}, volume = {68}, year = {2014}, }