@article{8235, abstract = {Due to large homology of human and canine EGFR, dogs suffering from spontaneous EGFR+ cancer can be considered as ideal translational models. Thereby, novel immunotherapeutic compounds can be developed for both human and veterinary patients. This study describes the radiolabeling of a canine anti-EGFR IgG antibody (can225IgG) with potential diagnostic and therapeutic value in comparative clinical settings. Can225IgG was functionalized with DTPA for subsequent chelation with the radionuclide 99mTc. Successful coupling of 10 DTPA molecules per antibody on average was proven by significant mass increase in MALDI-TOF spectroscopy, gel electrophoresis and immunoblots. Following functionalization and radiolabeling, 99mTc-DTPA-can225IgG fully retained its binding capacity towards human and canine EGFR in flow cytometry, immuno- and radioblots, and autoradiography. The affinity of radiolabeled can225IgG was determined to KD 0.8 ±0.0031 nM in a real-time kinetics assay on canine carcinoma cells by a competition binding technique. Stability tests of the radiolabeled compound identified TRIS buffered saline as the ideal formulation for short-term storage with 87.11 ±6.04% intact compound being still detected 60 minutes post radiolabeling. High stability, specificity and EGFR binding affinity pinpoint towards 99mTc-radiolabeled can225IgG antibody as an ideal lead compound for the first proof-of-concept diagnostic and therapeutic applications in canine cancer patients.}, author = {Fazekas-Singer, Judit and Berroterán-Infante, Neydher and Rami-Mark, Christina and Dumanic, Monika and Matz, Miroslawa and Willmann, Michael and Andreae, Fritz and Singer, Josef and Wadsak, Wolfgang and Mitterhauser, Markus and Jensen-Jarolim, Erika}, issn = {1949-2553}, journal = {Oncotarget}, pages = {83128--83141}, publisher = {Impact Journals}, title = {{Development of a radiolabeled caninized anti-EGFR antibody for comparative oncology trials}}, doi = {10.18632/oncotarget.20914}, volume = {8}, year = {2017}, } @article{825, abstract = {What data is needed about data? Describing the process to answer this question for the institutional data repository IST DataRep.}, author = {Petritsch, Barbara}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare}, number = {2}, pages = {200 -- 207}, publisher = {VÖB}, title = {{Metadata for research data in practice}}, doi = {10.31263/voebm.v70i2.1678}, volume = {70}, year = {2017}, } @inproceedings{8299, abstract = {Permissionless blockchain-based cryptocurrencies commonly use proof-of-work (PoW) or proof-of-stake (PoS) to ensure their security, e.g. to prevent double spending attacks. However, both approaches have disadvantages: PoW leads to massive amounts of wasted electricity and re-centralization, whereas major stakeholders in PoS might be able to create a monopoly. In this work, we propose proof-of-personhood (PoP), a mechanism that binds physical entities to virtual identities in a way that enables accountability while preserving anonymity. Afterwards we introduce PoPCoin, a new cryptocurrency, whose consensus mechanism leverages PoP to eliminate the dis-advantages of PoW and PoS while ensuring security. PoPCoin leads to a continuously fair and democratic wealth creation process which paves the way for an experimental basic income infrastructure.}, author = {Borge, Maria and Kokoris Kogias, Eleftherios and Jovanovic, Philipp and Gasser, Linus and Gailly, Nicolas and Ford, Bryan}, booktitle = {2017 IEEE European Symposium on Security and Privacy Workshops}, location = {Paris, France}, publisher = {IEEE}, title = {{Proof-of-personhood: Redemocratizing permissionless cryptocurrencies}}, doi = {10.1109/eurospw.2017.46}, year = {2017}, } @inproceedings{8306, abstract = {Bias-resistant public randomness is a critical component in many (distributed) protocols. Generating public randomness is hard, however, because active adversaries may behave dishonestly to bias public random choices toward their advantage. Existing solutions do not scale to hundreds or thousands of participants, as is needed in many decentralized systems. We propose two large-scale distributed protocols, RandHound and RandHerd, which provide publicly-verifiable, unpredictable, and unbiasable randomness against Byzantine adversaries. RandHound relies on an untrusted client to divide a set of randomness servers into groups for scalability, and it depends on the pigeonhole principle to ensure output integrity, even for non-random, adversarial group choices. RandHerd implements an efficient, decentralized randomness beacon. RandHerd is structurally similar to a BFT protocol, but uses RandHound in a one-time setup to arrange participants into verifiably unbiased random secret-sharing groups, which then repeatedly produce random output at predefined intervals. Our prototype demonstrates that RandHound and RandHerd achieve good performance across hundreds of participants while retaining a low failure probability by properly selecting protocol parameters, such as a group size and secret-sharing threshold. For example, when sharding 512 nodes into groups of 32, our experiments show that RandHound can produce fresh random output after 240 seconds. RandHerd, after a setup phase of 260 seconds, is able to generate fresh random output in intervals of approximately 6 seconds. For this configuration, both protocols operate at a failure probability of at most 0.08% against a Byzantine adversary.}, author = {Syta, E. and Jovanovic, P. and Kokoris Kogias, Eleftherios and Gailly, N. and Gasser, L. and Khoffi, I. and Fischer, M. J. and Ford, B.}, booktitle = {2017 IEEE Symposium on Security and Privacy}, isbn = {9781509055340}, issn = {2375-1207}, location = {San Jose, CA, United States}, pages = {444--460}, publisher = {IEEE}, title = {{Scalable bias-resistant distributed randomness}}, doi = {10.1109/SP.2017.45}, year = {2017}, } @inproceedings{8301, abstract = {Software-update mechanisms are critical to the security of modern systems, but their typically centralized design presents a lucrative and frequently attacked target. In this work, we propose CHAINIAC, a decentralized software-update framework that eliminates single points of failure, enforces transparency, and provides efficient verifiability of integrity and authenticity for software-release processes. Independent witness servers collectively verify conformance of software updates to release policies, build verifiers validate the source-to-binary correspondence, and a tamper-proof release log stores collectively signed updates, thus ensuring that no release is accepted by clients before being widely disclosed and validated. The release log embodies a skipchain, a novel data structure, enabling arbitrarily out-of-date clients to efficiently validate updates and signing keys. Evaluation of our CHAINIAC prototype on reproducible Debian packages shows that the automated update process takes the average of 5 minutes per release for individual packages, and only 20 seconds for the aggregate timeline. We further evaluate the framework using real-world data from the PyPI package repository and show that it offers clients security comparable to verifying every single update themselves while consuming only one-fifth of the bandwidth and having a minimal computational overhead.}, author = {Nikitin, Kirill and Kokoris Kogias, Eleftherios and Jovanovic, Philipp and Gasser, Linus and Gailly, Nicolas and Khoffi, Ismail and Cappos, Justin and Ford, Bryan}, booktitle = {Proceedings of the 26th USENIX Conference on Security Symposium}, isbn = {9781931971409}, location = {Vancouver, Canada}, pages = {1271–1287}, publisher = {USENIX Association}, title = {{CHAINIAC: Proactive software-update transparency via collectively signed skipchains and verified builds}}, year = {2017}, } @article{8446, abstract = {Solid‐state NMR spectroscopy can provide insight into protein structure and dynamics at the atomic level without inherent protein size limitations. However, a major hurdle to studying large proteins by solid‐state NMR spectroscopy is related to spectral complexity and resonance overlap, which increase with molecular weight and severely hamper the assignment process. Here the use of two sets of experiments is shown to expand the tool kit of 1H‐detected assignment approaches, which correlate a given amide pair either to the two adjacent CO–CA pairs (4D hCOCANH/hCOCAcoNH), or to the amide 1H of the neighboring residue (3D HcocaNH/HcacoNH, which can be extended to 5D). The experiments are based on efficient coherence transfers between backbone atoms using INEPT transfers between carbons and cross‐polarization for heteronuclear transfers. The utility of these experiments is exemplified with application to assemblies of deuterated, fully amide‐protonated proteins from approximately 20 to 60 kDa monomer, at magic‐angle spinning (MAS) frequencies from approximately 40 to 55 kHz. These experiments will also be applicable to protonated proteins at higher MAS frequencies. The resonance assignment of a domain within the 50.4 kDa bacteriophage T5 tube protein pb6 is reported, and this is compared to NMR assignments of the isolated domain in solution. This comparison reveals contacts of this domain to the core of the polymeric tail tube assembly.}, author = {Fraga, Hugo and Arnaud, Charles‐Adrien and Gauto, Diego F. and Audin, Maxime and Kurauskas, Vilius and Macek, Pavel and Krichel, Carsten and Guan, Jia‐Ying and Boisbouvier, Jerome and Sprangers, Remco and Breyton, Cécile and Schanda, Paul}, issn = {1439-4235}, journal = {ChemPhysChem}, keywords = {Physical and Theoretical Chemistry, Atomic and Molecular Physics, and Optics}, number = {19}, pages = {2697--2703}, publisher = {Wiley}, title = {{Solid‐state NMR H–N–(C)–H and H–N–C–C 3D/4D correlation experiments for resonance assignment of large proteins}}, doi = {10.1002/cphc.201700572}, volume = {18}, year = {2017}, } @article{8445, abstract = {Proteins perform their functions in solution but their structures are most frequently studied inside crystals. Here we probe how the crystal packing alters microsecond dynamics, using solid-state NMR measurements and multi-microsecond MD simulations of different crystal forms of ubiquitin. In particular, near-rotary-resonance relaxation dispersion (NERRD) experiments probe angular backbone motion, while Bloch–McConnell relaxation dispersion data report on fluctuations of the local electronic environment. These experiments and simulations reveal that the packing of the protein can significantly alter the thermodynamics and kinetics of local conformational exchange. Moreover, we report small-amplitude reorientational motion of protein molecules in the crystal lattice with an ~3–5° amplitude on a tens-of-microseconds time scale in one of the crystals, but not in others. An intriguing possibility arises that overall motion is to some extent coupled to local dynamics. Our study highlights the importance of considering the packing when analyzing dynamics of crystalline proteins.}, author = {Kurauskas, Vilius and Izmailov, Sergei A. and Rogacheva, Olga N. and Hessel, Audrey and Ayala, Isabel and Woodhouse, Joyce and Shilova, Anastasya and Xue, Yi and Yuwen, Tairan and Coquelle, Nicolas and Colletier, Jacques-Philippe and Skrynnikov, Nikolai R. and Schanda, Paul}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Slow conformational exchange and overall rocking motion in ubiquitin protein crystals}}, doi = {10.1038/s41467-017-00165-8}, volume = {8}, year = {2017}, } @article{8444, abstract = {Biophysical investigation of membrane proteins generally requires their extraction from native sources using detergents, a step that can lead, possibly irreversibly, to protein denaturation. The propensity of dodecylphosphocholine (DPC), a detergent widely utilized in NMR studies of membrane proteins, to distort their structure has been the subject of much controversy. It has been recently proposed that the binding specificity of the yeast mitochondrial ADP/ATP carrier (yAAC3) toward cardiolipins is preserved in DPC, thereby suggesting that DPC is a suitable environment in which to study membrane proteins. In this communication, we used all-atom molecular dynamics simulations to investigate the specific binding of cardiolipins to yAAC3. Our data demonstrate that the interaction interface observed in a native-like environment differs markedly from that inferred from an NMR investigation in DPC, implying that in this detergent, the protein structure is distorted. We further investigated yAAC3 solubilized in DPC and in the milder dodecylmaltoside with thermal-shift assays. The loss of thermal transition observed in DPC confirms that the protein is no longer properly folded in this environment.}, author = {Dehez, François and Schanda, Paul and King, Martin S. and Kunji, Edmund R.S. and Chipot, Christophe}, issn = {0006-3495}, journal = {Biophysical Journal}, keywords = {Biophysics}, number = {11}, pages = {2311--2315}, publisher = {Elsevier}, title = {{Mitochondrial ADP/ATP carrier in dodecylphosphocholine binds cardiolipins with non-native affinity}}, doi = {10.1016/j.bpj.2017.09.019}, volume = {113}, year = {2017}, } @article{9065, abstract = {Magnetic anisotropy in strontium iridate (Sr2IrO4) is found to be large because of the strong spin-orbit interactions. In our work, we studied the in-plane magnetic anisotropy of Sr2IrO4 and traced the anisotropic exchange interactions between the isospins in the crystal. The magnetic-field-dependent torque τ(H) showed a prominent transition from the canted antiferromagnetic state to the weak ferromagnetic (WFM) state. A comprehensive analysis was conducted to examine the isotropic and anisotropic regimes and probe the easy magnetization axis along the a b plane. The angle-dependent torque τ(θ) revealed a deviation from the sinusoidal behavior, and small differences in hysteresis were observed around 0° and 90° in the low-magnetic-field regime. This indicates that the orientation of the easy axis of the FM component is along the b axis, where the antiferromagnetic to WFM spin-flop transition occurs. We compared the coefficients of the magnetic susceptibility tensors and captured the anisotropy of the material. The in-plane τ(θ) revealed a tendency toward isotropic behavior for fields with values above the field value of the WFM transition.}, author = {Nauman, Muhammad and Hong, Yunjeong and Hussain, Tayyaba and Seo, M. S. and Park, S. Y. and Lee, N. and Choi, Y. J. and Kang, Woun and Jo, Younjung}, issn = {2469-9950}, journal = {Physical Review B}, number = {15}, publisher = {American Physical Society}, title = {{In-plane magnetic anisotropy in strontium iridate Sr2IrO4}}, doi = {10.1103/physrevb.96.155102}, volume = {96}, year = {2017}, } @article{9165, abstract = {Advances in colloidal synthesis allow for the design of particles with controlled patches. This article reviews routes towards colloidal locomotion, where energy is consumed and converted into motion, and its implementation with active patchy particles. A special emphasis is given to phoretic swimmers, where the self-propulsion originates from an interfacial phenomenon, raising experimental challenges and opening up opportunities for particles with controlled anisotropic surface chemistry and novel behaviors.}, author = {Aubret, A. and Ramananarivo, S. and Palacci, Jérémie A}, issn = {1359-0294}, journal = {Current Opinion in Colloid & Interface Science}, pages = {81--89}, publisher = {Elsevier}, title = {{Eppur si muove, and yet it moves: Patchy (phoretic) swimmers}}, doi = {10.1016/j.cocis.2017.05.007}, volume = {30}, year = {2017}, } @article{9190, abstract = {Plant meristems carry pools of continuously active stem cells, whose activity is controlled by developmental and environmental signals. After stem cell division, daughter cells that exit the stem cell domain acquire transit amplifying cell identity before they are incorporated into organs and differentiate. In this study, we used an integrated approach to elucidate the role of HECATE (HEC) genes in regulating developmental trajectories of shoot stem cells in Arabidopsis thaliana. Our work reveals that HEC function stabilizes cell fate in distinct zones of the shoot meristem thereby controlling the spatio-temporal dynamics of stem cell differentiation. Importantly, this activity is concomitant with the local modulation of cellular responses to cytokinin and auxin, two key phytohormones regulating cell behaviour. Mechanistically, we show that HEC factors transcriptionally control and physically interact with MONOPTEROS (MP), a key regulator of auxin signalling, and modulate the autocatalytic stabilization of auxin signalling output.}, author = {Gaillochet, Christophe and Stiehl, Thomas and Wenzl, Christian and Ripoll, Juan-José and Bailey-Steinitz, Lindsay J and Li, Lanxin and Pfeiffer, Anne and Miotk, Andrej and Hakenjos, Jana P and Forner, Joachim and Yanofsky, Martin F and Marciniak-Czochra, Anna and Lohmann, Jan U}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Control of plant cell fate transitions by transcriptional and hormonal signals}}, doi = {10.7554/elife.30135}, volume = {6}, year = {2017}, } @article{93, abstract = {An electro-optomechanical device capable of microwave-to-optics conversion has recently been demonstrated, with the vision of enabling optical networks of superconducting qubits. Here we present an improved converter design that uses a three-dimensional microwave cavity for coupling between the microwave transmission line and an integrated LC resonator on the converter chip. The new design simplifies the optical assembly and decouples it from the microwave part of the setup. Experimental demonstrations show that the modular device assembly allows us to flexibly tune the microwave coupling to the converter chip while maintaining small loss. We also find that electromechanical experiments are not impacted by the additional microwave cavity. Our design is compatible with a high-finesse optical cavity and will improve optical performance.}, author = {Menke, Tim and Burns, Peter and Higginbotham, Andrew P and Kampel, N S and Peterson, Robert and Cicak, Katarina and Simmonds, Raymond and Regal, Cindy and Lehnert, Konrad}, journal = {Review of Scientific Instruments}, number = {9}, publisher = {American Institute of Physics}, title = {{Reconfigurable re-entrant cavity for wireless coupling to an electro-optomechanical device}}, doi = {10.1063/1.5000973}, volume = {88}, year = {2017}, } @article{94, abstract = {We introduce a method for breaking Lorentz reciprocity based upon the noncommutation of frequency conversion and delay. The method requires no magnetic materials or resonant physics, allowing for the design of scalable and broadband nonreciprocal circuits. With this approach, two types of gyrators - universal building blocks for linear, nonreciprocal circuits - are constructed. Using one of these gyrators, we create a circulator with >15 dB of isolation across the 5-9 GHz band. Our designs may be readily extended to any platform with suitable frequency conversion elements, including semiconducting devices for telecommunication or an on-chip superconducting implementation for quantum information processing.}, author = {Rosenthal, Eric and Chapman, Benjamin and Higginbotham, Andrew P and Kerckhoff, Joseph and Lehnert, Konrad}, journal = {APS Physics, Physical Review Letters}, number = {14}, publisher = {American Physical Society}, title = {{Breaking Lorentz reciprocity with frequency conversion and delay}}, doi = {10.1103/PhysRevLett.119.147703}, volume = {119}, year = {2017}, } @article{9445, abstract = {Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.}, author = {Lyons, David B and Zilberman, Daniel}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes}}, doi = {10.7554/elife.30674}, volume = {6}, year = {2017}, } @inbook{957, abstract = {Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.}, author = {Clifton, Ben and Whitfield, Jason and Sanchez Romero, Inmaculada and Herde, Michel and Henneberger, Christian and Janovjak, Harald L and Jackson, Colin}, booktitle = {Synthetic Protein Switches}, editor = {Stein, Viktor}, issn = {10643745}, pages = {71 -- 87}, publisher = {Springer}, title = {{Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors}}, doi = {10.1007/978-1-4939-6940-1_5}, volume = {1596}, year = {2017}, } @article{9574, abstract = {Consider the sum X(ξ)=∑ni=1aiξi, where a=(ai)ni=1 is a sequence of non-zero reals and ξ=(ξi)ni=1 is a sequence of i.i.d. Rademacher random variables (that is, Pr[ξi=1]=Pr[ξi=−1]=1/2). The classical Littlewood-Offord problem asks for the best possible upper bound on the concentration probabilities Pr[X=x]. In this paper we study a resilience version of the Littlewood-Offord problem: how many of the ξi is an adversary typically allowed to change without being able to force concentration on a particular value? We solve this problem asymptotically, and present a few interesting open problems.}, author = {Bandeira, Afonso S. and Ferber, Asaf and Kwan, Matthew Alan}, issn = {1571-0653}, journal = {Electronic Notes in Discrete Mathematics}, pages = {93--99}, publisher = {Elsevier}, title = {{Resilience for the Littlewood-Offord problem}}, doi = {10.1016/j.endm.2017.06.025}, volume = {61}, year = {2017}, } @article{9590, abstract = {We show that for any fixed dense graph G and bounded-degree tree T on the same number of vertices, a modest random perturbation of G will typically contain a copy of T . This combines the viewpoints of the well-studied problems of embedding trees into fixed dense graphs and into random graphs, and extends a sizeable body of existing research on randomly perturbed graphs. Specifically, we show that there is c=c(α,Δ) such that if G is an n-vertex graph with minimum degree at least αn, and T is an n-vertex tree with maximum degree at most Δ , then if we add cn uniformly random edges to G, the resulting graph will contain T asymptotically almost surely (as n→∞ ). Our proof uses a lemma concerning the decomposition of a dense graph into super-regular pairs of comparable sizes, which may be of independent interest.}, author = {Krivelevich, Michael and Kwan, Matthew Alan and Sudakov, Benny}, issn = {1095-7146}, journal = {SIAM Journal on Discrete Mathematics}, number = {1}, pages = {155--171}, publisher = {Society for Industrial & Applied Mathematics}, title = {{Bounded-degree spanning trees in randomly perturbed graphs}}, doi = {10.1137/15m1032910}, volume = {31}, year = {2017}, } @article{9588, abstract = {Consider the sum X(ξ)=∑ni=1aiξi , where a=(ai)ni=1 is a sequence of non-zero reals and ξ=(ξi)ni=1 is a sequence of i.i.d. Rademacher random variables (that is, Pr[ξi=1]=Pr[ξi=−1]=1/2 ). The classical Littlewood-Offord problem asks for the best possible upper bound on the concentration probabilities Pr[X=x] . In this paper we study a resilience version of the Littlewood-Offord problem: how many of the ξi is an adversary typically allowed to change without being able to force concentration on a particular value? We solve this problem asymptotically, and present a few interesting open problems.}, author = {Bandeira, Afonso S. and Ferber, Asaf and Kwan, Matthew Alan}, issn = {0001-8708}, journal = {Advances in Mathematics}, pages = {292--312}, publisher = {Elsevier}, title = {{Resilience for the Littlewood–Offord problem}}, doi = {10.1016/j.aim.2017.08.031}, volume = {319}, year = {2017}, } @article{9589, abstract = {We give an asymptotic expression for the expected number of spanning trees in a random graph with a given degree sequence , provided that the number of edges is at least , where is the maximum degree. A key part of our argument involves establishing a concentration result for a certain family of functions over random trees with given degrees, using Prüfer codes.}, author = {Greenhill, Catherine and Isaev, Mikhail and Kwan, Matthew Alan and McKay, Brendan D.}, issn = {0195-6698}, journal = {European Journal of Combinatorics}, pages = {6--25}, publisher = {Elsevier}, title = {{The average number of spanning trees in sparse graphs with given degrees}}, doi = {10.1016/j.ejc.2017.02.003}, volume = {63}, year = {2017}, } @inproceedings{963, abstract = {Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed. }, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {18688969}, location = {Aalborg, Denmark}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Timed network games with clocks}}, doi = {10.4230/LIPIcs.MFCS.2017.37}, volume = {83}, year = {2017}, } @misc{9709, abstract = {Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.}, author = {Prentice, Jason and Marre, Olivier and Ioffe, Mark and Loback, Adrianna and Tkačik, Gašper and Berry, Michael}, publisher = {Dryad}, title = {{Data from: Error-robust modes of the retinal population code}}, doi = {10.5061/dryad.1f1rc}, year = {2017}, } @article{541, abstract = {While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, issn = {15537390}, journal = {PLoS Genetics}, number = {12}, publisher = {Public Library of Science}, title = {{Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations}}, doi = {10.1371/journal.pgen.1007122}, volume = {13}, year = {2017}, } @misc{9847, abstract = {information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data}, author = {Pleska, Maros and Guet, Calin C}, publisher = {The Royal Society}, title = {{Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification}}, doi = {10.6084/m9.figshare.5633917.v1}, year = {2017}, } @misc{9845, abstract = {Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured in single cells}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Mathematical model}}, doi = {10.1371/journal.pgen.1007122.s017}, year = {2017}, } @misc{9849, abstract = {This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Modelling and simulation details}}, doi = {10.1371/journal.pcbi.1005609.s001}, year = {2017}, } @misc{9850, abstract = {In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Extensions of the model}}, doi = {10.1371/journal.pcbi.1005609.s002}, year = {2017}, } @misc{9846, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Supplementary methods}}, doi = {10.1371/journal.pgen.1007122.s016}, year = {2017}, } @article{680, abstract = {In order to respond reliably to specific features of their environment, sensory neurons need to integrate multiple incoming noisy signals. Crucially, they also need to compete for the interpretation of those signals with other neurons representing similar features. The form that this competition should take depends critically on the noise corrupting these signals. In this study we show that for the type of noise commonly observed in sensory systems, whose variance scales with the mean signal, sensory neurons should selectively divide their input signals by their predictions, suppressing ambiguous cues while amplifying others. Any change in the stimulus context alters which inputs are suppressed, leading to a deep dynamic reshaping of neural receptive fields going far beyond simple surround suppression. Paradoxically, these highly variable receptive fields go alongside and are in fact required for an invariant representation of external sensory features. In addition to offering a normative account of context-dependent changes in sensory responses, perceptual inference in the presence of signal-dependent noise accounts for ubiquitous features of sensory neurons such as divisive normalization, gain control and contrast dependent temporal dynamics.}, author = {Chalk, Matthew J and Masset, Paul and Gutkin, Boris and Denève, Sophie}, issn = {1553734X}, journal = {PLoS Computational Biology}, number = {6}, publisher = {Public Library of Science}, title = {{Sensory noise predicts divisive reshaping of receptive fields}}, doi = {10.1371/journal.pcbi.1005582}, volume = {13}, year = {2017}, } @misc{9851, abstract = {Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Heuristic prediction for multiple stresses}}, doi = {10.1371/journal.pcbi.1005609.s003}, year = {2017}, } @misc{9852, abstract = {We show how different combination strategies affect the fraction of individuals that are multi-resistant.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Resistance frequencies for different combination strategies}}, doi = {10.1371/journal.pcbi.1005609.s004}, year = {2017}, } @misc{9855, abstract = {Includes derivation of optimal estimation algorithm, generalisation to non-poisson noise statistics, correlated input noise, and implementation of in a multi-layer neural network.}, author = {Chalk, Matthew J and Masset, Paul and Gutkin, Boris and Denève, Sophie}, publisher = {Public Library of Science}, title = {{Supplementary appendix}}, doi = {10.1371/journal.pcbi.1005582.s001}, year = {2017}, } @article{8423, abstract = {In this paper we show that for a generic strictly convex domain, one can recover the eigendata corresponding to Aubry–Mather periodic orbits of the induced billiard map from the (maximal) marked length spectrum of the domain.}, author = {Huang, Guan and Kaloshin, Vadim and Sorrentino, Alfonso}, issn = {0012-7094}, journal = {Duke Mathematical Journal}, number = {1}, pages = {175--209}, publisher = {Duke University Press}, title = {{On the marked length spectrum of generic strictly convex billiard tables}}, doi = {10.1215/00127094-2017-0038}, volume = {167}, year = {2017}, } @article{8427, abstract = {We show that any sufficiently (finitely) smooth ℤ₂-symmetric strictly convex domain sufficiently close to a circle is dynamically spectrally rigid; i.e., all deformations among domains in the same class that preserve the length of all periodic orbits of the associated billiard flow must necessarily be isometric deformations. This gives a partial answer to a question of P. Sarnak.}, author = {De Simoi, Jacopo and Kaloshin, Vadim and Wei, Qiaoling}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {1}, pages = {277--314}, publisher = {Annals of Mathematics}, title = {{Dynamical spectral rigidity among Z2-symmetric strictly convex domains close to a circle}}, doi = {10.4007/annals.2017.186.1.7}, volume = {186}, year = {2017}, } @article{8449, abstract = {Ensuring the correct folding of RNA molecules in the cell is of major importance for a large variety of biological functions. Therefore, chaperone proteins that assist RNA in adopting their functionally active states are abundant in all living organisms. An important feature of RNA chaperone proteins is that they do not require an external energy source to perform their activity, and that they interact transiently and non-specifically with their RNA targets. So far, little is known about the mechanistic details of the RNA chaperone activity of these proteins. Prominent examples of RNA chaperones are bacterial cold shock proteins (Csp) that have been reported to bind single-stranded RNA and DNA. Here, we have used advanced NMR spectroscopy techniques to investigate at atomic resolution the RNA-melting activity of CspA, the major cold shock protein of Escherichia coli, upon binding to different RNA hairpins. Real-time NMR provides detailed information on the folding kinetics and folding pathways. Finally, comparison of wild-type CspA with single-point mutants and small peptides yields insights into the complementary roles of aromatic and positively charged amino-acid side chains for the RNA chaperone activity of the protein.}, author = {Rennella, Enrico and Sára, Tomáš and Juen, Michael and Wunderlich, Christoph and Imbert, Lionel and Solyom, Zsofia and Favier, Adrien and Ayala, Isabel and Weinhäupl, Katharina and Schanda, Paul and Konrat, Robert and Kreutz, Christoph and Brutscher, Bernhard}, issn = {0305-1048}, journal = {Nucleic Acids Research}, number = {7}, pages = {4255--4268}, publisher = {Oxford University Press}, title = {{RNA binding and chaperone activity of the E.coli cold-shock protein CspA}}, doi = {10.1093/nar/gkx044}, volume = {45}, year = {2017}, } @article{8447, abstract = {Solid-state NMR spectroscopy can provide site-resolved information about protein dynamics over many time scales. Here we combine protein deuteration, fast magic-angle spinning (~45–60 kHz) and proton detection to study dynamics of ubiquitin in microcrystals, and in particular a mutant in a region that undergoes microsecond motions in a β-turn region in the wild-type protein. We use 15N R1ρ relaxation measurements as a function of the radio-frequency (RF) field strength, i.e. relaxation dispersion, to probe how the G53A mutation alters these dynamics. We report a population-inversion of conformational states: the conformation that in the wild-type protein is populated only sparsely becomes the predominant state. We furthermore explore the potential to use amide-1H R1ρ relaxation to obtain insight into dynamics. We show that while quantitative interpretation of 1H relaxation remains beyond reach under the experimental conditions, due to coherent contributions to decay, one may extract qualitative information about flexibility.}, author = {Gauto, Diego F. and Hessel, Audrey and Rovó, Petra and Kurauskas, Vilius and Linser, Rasmus and Schanda, Paul}, issn = {0926-2040}, journal = {Solid State Nuclear Magnetic Resonance}, keywords = {Nuclear and High Energy Physics, Instrumentation, General Chemistry, Radiation}, number = {10}, pages = {86--95}, publisher = {Elsevier}, title = {{Protein conformational dynamics studied by 15N and 1HR1ρ relaxation dispersion: Application to wild-type and G53A ubiquitin crystals}}, doi = {10.1016/j.ssnmr.2017.04.002}, volume = {87}, year = {2017}, } @article{8448, abstract = {We present an improved fast mixing device based on the rapid mixing of two solutions inside the NMR probe, as originally proposed by Hore and coworkers (J. Am. Chem. Soc. 125 (2003) 12484–12492). Such a device is important for off-equilibrium studies of molecular kinetics by multidimensional real-time NMR spectrsocopy. The novelty of this device is that it allows removing the injector from the NMR detection volume after mixing, and thus provides good magnetic field homogeneity independently of the initial sample volume placed in the NMR probe. The apparatus is simple to build, inexpensive, and can be used without any hardware modification on any type of liquid-state NMR spectrometer. We demonstrate the performance of our fast mixing device in terms of improved magnetic field homogeneity, and show an application to the study of protein folding and the structural characterization of transiently populated folding intermediates.}, author = {Franco, Rémi and Favier, Adrien and Schanda, Paul and Brutscher, Bernhard}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, keywords = {Nuclear and High Energy Physics, Biophysics, Biochemistry, Condensed Matter Physics}, number = {8}, pages = {125--129}, publisher = {Elsevier}, title = {{Optimized fast mixing device for real-time NMR applications}}, doi = {10.1016/j.jmr.2017.05.016}, volume = {281}, year = {2017}, } @article{8451, abstract = {The structure, dynamics, and function of membrane proteins are intimately linked to the properties of the membrane environment in which the proteins are embedded. For structural and biophysical characterization, membrane proteins generally need to be extracted from the membrane and reconstituted in a suitable membrane‐mimicking environment. Ensuring functional and structural integrity in these environments is often a major concern. The styrene/maleic acid co‐polymer has recently been shown to be able to extract lipid/membrane protein patches directly from native membranes to form nanosize discoidal proteolipid particles, also referred to as native nanodiscs. In this work, we show that high‐resolution solid‐state NMR spectra can be obtained from an integral membrane protein in native nanodiscs, as exemplified by the 2×34 kDa bacterial cation diffusion facilitator CzcD.}, author = {Bersch, Beate and Dörr, Jonas M. and Hessel, Audrey and Killian, J. Antoinette and Schanda, Paul}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {9}, pages = {2508--2512}, publisher = {Wiley}, title = {{Proton-detected solid-state NMR spectroscopy of a Zinc diffusion facilitator protein in native nanodiscs}}, doi = {10.1002/anie.201610441}, volume = {56}, year = {2017}, } @inbook{8450, abstract = {Methyl groups are very useful probes of structure, dynamics, and interactions in protein NMR spectroscopy. In particular, methyl-directed experiments provide high sensitivity even in very large proteins, such as membrane proteins in a membrane-mimicking environment. In this chapter, we discuss the approach for labeling methyl groups in E. coli-based protein expression, as exemplified with the mitochondrial carrier GGC.}, author = {Kurauskas, Vilius and Schanda, Paul and Sounier, Remy}, booktitle = {Membrane protein structure and function characterization}, isbn = {9781493971497}, issn = {1064-3745}, pages = {109--123}, publisher = {Springer Nature}, title = {{Methyl-specific isotope labeling strategies for NMR studies of membrane proteins}}, doi = {10.1007/978-1-4939-7151-0_6}, volume = {1635}, year = {2017}, } @article{9137, abstract = {Pools of air cooled by partial rain evaporation span up to several hundreds of kilometers in nature and typically last less than 1 day, ultimately losing their identity to the large-scale flow. These fundamentally differ in character from the radiatively-driven dry pools defining convective aggregation. Advancement in remote sensing and in computer capabilities has promoted exploration of how precipitation-induced cold pool processes modify the convective spectrum and life cycle. This contribution surveys current understanding of such cold pools over the tropical and subtropical oceans. In shallow convection with low rain rates, the cold pools moisten, preserving the near-surface equivalent potential temperature or increasing it if the surface moisture fluxes cannot ventilate beyond the new surface layer; both conditions indicate downdraft origin air from within the boundary layer. When rain rates exceed ∼ 2 mm h−1, convective-scale downdrafts can bring down drier air of lower equivalent potential temperature from above the boundary layer. The resulting density currents facilitate the lifting of locally thermodynamically favorable air and can impose an arc-shaped mesoscale cloud organization. This organization allows clouds capable of reaching 4–5 km within otherwise dry environments. These are more commonly observed in the northern hemisphere trade wind regime, where the flow to the intertropical convergence zone is unimpeded by the equator. Their near-surface air properties share much with those shown from cold pools sampled in the equatorial Indian Ocean. Cold pools are most effective at influencing the mesoscale organization when the atmosphere is moist in the lower free troposphere and dry above, suggesting an optimal range of water vapor paths. Outstanding questions on the relationship between cold pools, their accompanying moisture distribution and cloud cover are detailed further. Near-surface water vapor rings are documented in one model inside but near the cold pool edge; these are not consistent with observations, but do improve with smaller horizontal grid spacings.}, author = {Zuidema, Paquita and Torri, Giuseppe and Muller, Caroline J and Chandra, Arunchandra}, issn = {0169-3298}, journal = {Surveys in Geophysics}, keywords = {Geochemistry and Petrology, Geophysics}, number = {6}, pages = {1283--1305}, publisher = {Springer Nature}, title = {{A survey of precipitation-induced atmospheric cold pools over oceans and their interactions with the larger-scale environment}}, doi = {10.1007/s10712-017-9447-x}, volume = {38}, year = {2017}, } @article{9138, abstract = {Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.}, author = {Holloway, Christopher E. and Wing, Allison A. and Bony, Sandrine and Muller, Caroline J and Masunaga, Hirohiko and L’Ecuyer, Tristan S. and Turner, David D. and Zuidema, Paquita}, issn = {0169-3298}, journal = {Surveys in Geophysics}, keywords = {Geochemistry and Petrology, Geophysics}, number = {6}, pages = {1199--1236}, publisher = {Springer Nature}, title = {{Observing convective aggregation}}, doi = {10.1007/s10712-017-9419-1}, volume = {38}, year = {2017}, } @article{9139, abstract = {Organized convection in the tropics occurs across a range of spatial and temporal scales and strongly influences cloud cover and humidity. One mode of organization found is “self-aggregation,” in which moist convection spontaneously organizes into one or several isolated clusters despite spatially homogeneous boundary conditions and forcing. Self-aggregation is driven by interactions between clouds, moisture, radiation, surface fluxes, and circulation, and occurs in a wide variety of idealized simulations of radiative–convective equilibrium. Here we provide a review of convective self-aggregation in numerical simulations, including its character, causes, and effects. We describe the evolution of self-aggregation including its time and length scales and the physical mechanisms leading to its triggering and maintenance, and we also discuss possible links to climate and climate change.}, author = {Wing, Allison A. and Emanuel, Kerry and Holloway, Christopher E. and Muller, Caroline J}, issn = {0169-3298}, journal = {Surveys in Geophysics}, keywords = {Geochemistry and Petrology, Geophysics}, number = {6}, pages = {1173--1197}, publisher = {Springer Nature}, title = {{Convective self-aggregation in numerical simulations: A review}}, doi = {10.1007/s10712-017-9408-4}, volume = {38}, year = {2017}, } @article{9152, abstract = {Previous numerical studies of the dissipation of internal tides in idealized settings suggest the existence of a critical latitude (~29°) where dissipation is enhanced. But observations only indicate a modest enhancement at this latitude. To resolve this difference between observational and numerical results, the authors study the latitudinal dependence of internal tides’ dissipation in more realistic conditions. In particular, the ocean is not a quiescent medium; the presence of large-scale currents or mesoscale eddies can impact the propagation and dissipation of internal tides. This paper investigates the impact of a weak background mean current in numerical simulations. The authors focus on the local dissipation of high spatial mode internal waves near their generation site. The vertical profile of dissipation and its variation with latitude without the mean current are consistent with earlier studies. But adding a weak mean current has a major impact on the latitudinal distribution of dissipation. The peak at the critical latitude disappears, and the dissipation is closer to a constant, albeit with two weak peaks at ~25° and ~35° latitude. This disappearance results from the Doppler shift of the internal tides’ frequency, which hinders the nonlinear transfer of energy to small-scale secondary waves via the parametric subharmonic instability (PSI). The new two weak peaks correspond to the Doppler-shifted critical latitudes of the left- and right-propagating waves. The results are confirmed in simulations with simple sinusoidal topography. Thus, although nonlinear transfers via PSI are efficient at dissipating internal tides, the exact location of the dissipation is sensitive to large-scale oceanic conditions.}, author = {Richet, O. and Muller, Caroline J and Chomaz, J.-M.}, issn = {0022-3670}, journal = {Journal of Physical Oceanography}, keywords = {Oceanography}, number = {6}, pages = {1457--1472}, publisher = {American Meteorological Society}, title = {{Impact of a mean current on the internal tide energy dissipation at the critical latitude}}, doi = {10.1175/jpo-d-16-0197.1}, volume = {47}, year = {2017}, } @article{934, abstract = {During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that morphogenesis is driven by proliferative terminal end buds that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network. We show that the majority of terminal end bud cells function as highly proliferative, lineage-committed MaSCs that are heterogeneous in their expression profile and short-term contribution to ductal extension. Yet, through cell rearrangements during terminal end bud bifurcation, each MaSC is able to contribute actively to long-term growth. Our study shows that the behaviour of MaSCs is not directly linked to a single expression profile. Instead, morphogenesis relies upon lineage-restricted heterogeneous MaSC populations that function as single equipotent pools in the long term.}, author = {Scheele, Colinda and Hannezo, Edouard B and Muraro, Mauro and Zomer, Anoek and Langedijk, Nathalia and Van Oudenaarden, Alexander and Simons, Benjamin and Van Rheenen, Jacco}, issn = {00280836}, journal = {Nature}, number = {7641}, pages = {313 -- 317}, publisher = {Nature Publishing Group}, title = {{Identity and dynamics of mammary stem cells during branching morphogenesis}}, doi = {10.1038/nature21046}, volume = {542}, year = {2017}, } @article{936, abstract = {Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain. Analysis of cell shapes suggests that RhoA alters the balance of forces exerted on the MCC apical surface. Finally, quantitative time-lapse imaging and fluorescence recovery after photobleaching studies argue that RhoA works in concert with Fmn1 to control assembly of the specialized apical actin network in MCCs. These data provide new molecular insights into epithelial apical surface assembly and could also shed light on mechanisms of apical lumen formation}, author = {Sedzinski, Jakub and Hannezo, Edouard B and Tu, Fan and Biro, Maté and Wallingford, John}, journal = {Journal of Cell Science}, number = {5}, publisher = {Company of Biologists}, title = {{RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells }}, doi = {10.1242/jcs.202234}, volume = {130}, year = {2017}, } @article{937, abstract = {During epithelial cytokinesis, the remodelling of adhesive cell-cell contacts between the dividing cell and its neighbours has profound implications for the integrity, arrangement and morphogenesis of proliferative tissues. In both vertebrates and invertebrates, this remodelling requires the activity of non-muscle myosin II (MyoII) in the interphasic cells neighbouring the dividing cell. However, the mechanisms that coordinate cytokinesis and MyoII activity in the neighbours are unknown. Here we show that in the Drosophila notum epithelium, each cell division is associated with a mechanosensing and transmission event that controls MyoII dynamics in neighbouring cells. We find that the ring pulling forces promote local junction elongation, which results in local E-cadherin dilution at the ingressing adherens junction. In turn, the reduction in E-cadherin concentration and the contractility of the neighbouring cells promote self-organized actomyosin flows, ultimately leading to accumulation of MyoII at the base of the ingressing junction. Although force transduction has been extensively studied in the context of adherens junction reinforcement to stabilize adhesive cell-cell contacts, we propose an alternative mechanosensing mechanism that coordinates actomyosin dynamics between epithelial cells and sustains the remodelling of the adherens junction in response to mechanical forces.}, author = {Pinheiro, Diana and Hannezo, Edouard B and Herszterg, Sophie and Bosveld, Floris and Gaugué, Isabelle and Balakireva, Maria and Wang, Zhimin and Cristo, Inês and Rigaud, Stéphane and Markova, Olga and Bellaïche, Yohanns}, issn = {00280836}, journal = {Nature}, number = {7652}, pages = {103 -- 107}, publisher = {Nature Publishing Group}, title = {{Transmission of cytokinesis forces via E cadherin dilution and actomyosin flows}}, doi = {10.1038/nature22041}, volume = {545}, year = {2017}, } @inproceedings{941, abstract = {Recently there has been a proliferation of automated program repair (APR) techniques, targeting various programming languages. Such techniques can be generally classified into two families: syntactic- and semantics-based. Semantics-based APR, on which we focus, typically uses symbolic execution to infer semantic constraints and then program synthesis to construct repairs conforming to them. While syntactic-based APR techniques have been shown successful on bugs in real-world programs written in both C and Java, semantics-based APR techniques mostly target C programs. This leaves empirical comparisons of the APR families not fully explored, and developers without a Java-based semantics APR technique. We present JFix, a semantics-based APR framework that targets Java, and an associated Eclipse plugin. JFix is implemented atop Symbolic PathFinder, a well-known symbolic execution engine for Java programs. It extends one particular APR technique (Angelix), and is designed to be sufficiently generic to support a variety of such techniques. We demonstrate that semantics-based APR can indeed efficiently and effectively repair a variety of classes of bugs in large real-world Java programs. This supports our claim that the framework can both support developers seeking semantics-based repair of bugs in Java programs, as well as enable larger scale empirical studies comparing syntactic- and semantics-based APR targeting Java. The demonstration of our tool is available via the project website at: https://xuanbachle.github.io/semanticsrepair/ }, author = {Le, Xuan and Chu, Duc Hiep and Lo, David and Le Goues, Claire and Visser, Willem}, booktitle = {Proceedings of the 26th ACM SIGSOFT International Symposium on Software Testing and Analysis}, location = {Santa Barbara, CA, United States}, pages = {376 -- 379 }, publisher = {ACM}, title = {{JFIX: Semantics-based repair of Java programs via symbolic PathFinder}}, doi = {10.1145/3092703.3098225}, year = {2017}, } @article{9506, abstract = {Methylation in the bodies of active genes is common in animals and vascular plants. Evolutionary patterns indicate homeostatic functions for this type of methylation.}, author = {Zilberman, Daniel}, issn = {1465-6906}, journal = {Genome Biology}, number = {1}, publisher = {Springer Nature}, title = {{An evolutionary case for functional gene body methylation in plants and animals}}, doi = {10.1186/s13059-017-1230-2}, volume = {18}, year = {2017}, } @inbook{958, abstract = {Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors.}, author = {Mitchell, Joshua and Zhang, William and Herde, Michel and Henneberger, Christian and Janovjak, Harald L and O'Mara, Megan and Jackson, Colin}, booktitle = {Synthetic Protein Switches}, editor = {Stein, Viktor}, issn = {10643745}, pages = {89 -- 99}, publisher = {Springer}, title = {{Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment}}, doi = {10.1007/978-1-4939-6940-1_6}, volume = {1596}, year = {2017}, } @article{9660, abstract = {In this paper we discuss how the information contained in atomistic simulations of homogeneous nucleation should be used when fitting the parameters in macroscopic nucleation models. We show how the number of solid and liquid atoms in such simulations can be determined unambiguously by using a Gibbs dividing surface and how the free energy as a function of the number of solid atoms in the nucleus can thus be extracted. We then show that the parameters (the chemical potential, the interfacial free energy, and a Tolman correction) of a model based on classical nucleation theory can be fitted using the information contained in these free-energy profiles but that the parameters in such models are highly correlated. This correlation is unfortunate as it ensures that small errors in the computed free energy surface can give rise to large errors in the extrapolated properties of the fitted model. To resolve this problem we thus propose a method for fitting macroscopic nucleation models that uses simulations of planar interfaces and simulations of three-dimensional nuclei in tandem. We show that when the chemical potentials and the interface energy are pinned to their planar-interface values, more precise estimates for the Tolman length are obtained. Extrapolating the free energy profile obtained from small simulation boxes to larger nuclei is thus more reliable.}, author = {Cheng, Bingqing and Tribello, Gareth A. and Ceriotti, Michele}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, number = {10}, publisher = {AIP Publishing}, title = {{The Gibbs free energy of homogeneous nucleation: From atomistic nuclei to the planar limit}}, doi = {10.1063/1.4997180}, volume = {147}, year = {2017}, } @article{9661, abstract = {Macroscopic theories of nucleation such as classical nucleation theory envision that clusters of the bulk stable phase form inside the bulk metastable phase. Molecular dynamics simulations are often used to elucidate nucleation mechanisms, by capturing the microscopic configurations of all the atoms. In this paper, we introduce a thermodynamic model that links macroscopic theories and atomic-scale simulations and thus provide a simple and elegant framework for testing the limits of classical nucleation theory.}, author = {Cheng, Bingqing and Ceriotti, Michele}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, number = {3}, publisher = {AIP Publishing}, title = {{Bridging the gap between atomistic and macroscopic models of homogeneous nucleation}}, doi = {10.1063/1.4973883}, volume = {146}, year = {2017}, }