TY - JOUR
AB - Pursuing the similarity between the Kontsevich-Soibelman construction of the cohomological Hall algebra (CoHA) of BPS states and Lusztig's construction of canonical bases for quantum enveloping algebras, and the similarity between the integrality conjecture for motivic Donaldson-Thomas invariants and the PBW theorem for quantum enveloping algebras, we build a coproduct on the CoHA associated to a quiver with potential. We also prove a cohomological dimensional reduction theorem, further linking a special class of CoHAs with Yangians, and explaining how to connect the study of character varieties with the study of CoHAs.
AU - Davison, Ben
ID - 687
IS - 2
JF - Quarterly Journal of Mathematics
SN - 00335606
TI - The critical CoHA of a quiver with potential
VL - 68
ER -
TY - CONF
AB - We show that the framework of topological data analysis can be extended from metrics to general Bregman divergences, widening the scope of possible applications. Examples are the Kullback - Leibler divergence, which is commonly used for comparing text and images, and the Itakura - Saito divergence, popular for speech and sound. In particular, we prove that appropriately generalized čech and Delaunay (alpha) complexes capture the correct homotopy type, namely that of the corresponding union of Bregman balls. Consequently, their filtrations give the correct persistence diagram, namely the one generated by the uniformly growing Bregman balls. Moreover, we show that unlike the metric setting, the filtration of Vietoris-Rips complexes may fail to approximate the persistence diagram. We propose algorithms to compute the thus generalized čech, Vietoris-Rips and Delaunay complexes and experimentally test their efficiency. Lastly, we explain their surprisingly good performance by making a connection with discrete Morse theory.
AU - Edelsbrunner, Herbert
AU - Wagner, Hubert
ID - 688
SN - 18688969
TI - Topological data analysis with Bregman divergences
VL - 77
ER -
TY - JOUR
AB - Rett syndrome modeling in monkey mirrors the human disorder.
AU - Novarino, Gaia
ID - 689
IS - 393
JF - Science Translational Medicine
SN - 19466234
TI - Rett syndrome modeling goes simian
VL - 9
ER -
TY - JOUR
AB - Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels.
AU - Miki, Takafumi
AU - Kaufmann, Walter
AU - Malagon, Gerardo
AU - Gomez, Laura
AU - Tabuchi, Katsuhiko
AU - Watanabe, Masahiko
AU - Shigemoto, Ryuichi
AU - Marty, Alain
ID - 693
IS - 26
JF - PNAS
SN - 00278424
TI - Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses
VL - 114
ER -
TY - JOUR
AB - A change regarding the extent of adhesion - hereafter referred to as adhesion plasticity - between adhesive and less-adhesive states of mammalian cells is important for their behavior. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma cells growing in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By using transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and protein levels in suspension cells. Furthermore, by transiently challenging breast cancer cells to grow under non-adherent conditions markedly reduces Tns3 protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental MDA-MB-468 cells results in defective adhesion, spreading and migration. Tns3-knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 protein expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a crucial focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.
AU - Veß, Astrid
AU - Blache, Ulrich
AU - Leitner, Laura
AU - Kurz, Angela
AU - Ehrenpfordt, Anja
AU - Sixt, Michael K
AU - Posern, Guido
ID - 694
IS - 13
JF - Journal of Cell Science
SN - 00219533
TI - A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity
VL - 130
ER -
TY - CONF
AB - De, Trevisan and Tulsiani [CRYPTO 2010] show that every distribution over n-bit strings which has constant statistical distance to uniform (e.g., the output of a pseudorandom generator mapping n-1 to n bit strings), can be distinguished from the uniform distribution with advantage epsilon by a circuit of size O( 2^n epsilon^2). We generalize this result, showing that a distribution which has less than k bits of min-entropy, can be distinguished from any distribution with k bits of delta-smooth min-entropy with advantage epsilon by a circuit of size O(2^k epsilon^2/delta^2). As a special case, this implies that any distribution with support at most 2^k (e.g., the output of a pseudoentropy generator mapping k to n bit strings) can be distinguished from any given distribution with min-entropy k+1 with advantage epsilon by a circuit of size O(2^k epsilon^2). Our result thus shows that pseudoentropy distributions face basically the same non-uniform attacks as pseudorandom distributions.
AU - Pietrzak, Krzysztof Z
AU - Skórski, Maciej
ID - 697
SN - 18688969
TI - Non uniform attacks against pseudoentropy
VL - 80
ER -
TY - JOUR
AB - Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases.
AU - Wang, Yejun
AU - Nagarajan, Mallika
AU - Uhler, Caroline
AU - Shivashankar, Gv
ID - 698
IS - 14
JF - Molecular Biology of the Cell
SN - 10591524
TI - Orientation and repositioning of chromosomes correlate with cell geometry dependent gene expression
VL - 28
ER -
TY - JOUR
AB - In antagonistic symbioses, such as host–parasite interactions, one population’s success is the other’s loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the “Red Queen effect”), but disfavored in certain mutualistic symbioses (the “Red King effect”). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts.
AU - Veller, Carl
AU - Hayward, Laura
AU - Nowak, Martin
AU - Hilbe, Christian
ID - 699
IS - 27
JF - PNAS
SN - 00278424
TI - The red queen and king in finite populations
VL - 114
ER -
TY - JOUR
AB - Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology. The center frequency and line width of the transparency peak give the resonance frequency and damping rate of the microtubule, respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method opens the new possibilities to gain information about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs.
AU - Barzanjeh, Shabir
AU - Salari, Vahid
AU - Tuszynski, Jack
AU - Cifra, Michal
AU - Simon, Christoph
ID - 700
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Optomechanical proposal for monitoring microtubule mechanical vibrations
VL - 96
ER -
TY - JOUR
AB - A d-dimensional simplex S is called a k-reptile (or a k-reptile simplex) if it can be tiled by k simplices with disjoint interiors that are all mutually congruent and similar to S. For d = 2, triangular k-reptiles exist for all k of the form a^2, 3a^2 or a^2+b^2 and they have been completely characterized by Snover, Waiveris, and Williams. On the other hand, the only k-reptile simplices that are known for d ≥ 3, have k = m^d, where m is a positive integer. We substantially simplify the proof by Matoušek and the second author that for d = 3, k-reptile tetrahedra can exist only for k = m^3. We then prove a weaker analogue of this result for d = 4 by showing that four-dimensional k-reptile simplices can exist only for k = m^2.
AU - Kynčl, Jan
AU - Patakova, Zuzana
ID - 701
IS - 3
JF - The Electronic Journal of Combinatorics
SN - 10778926
TI - On the nonexistence of k reptile simplices in ℝ^3 and ℝ^4
VL - 24
ER -
TY - JOUR
AB - Leading autism-associated mutation in mouse partially mimics human disorder.
AU - Novarino, Gaia
ID - 702
IS - 399
JF - Science Translational Medicine
SN - 19466234
TI - The riddle of CHD8 haploinsufficiency in autism spectrum disorder
VL - 9
ER -
TY - JOUR
AB - A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse.
AU - Geng, Xiaoqi
AU - Maruo, Tomohiko
AU - Mandai, Kenji
AU - Supriyanto, Irwan
AU - Miyata, Muneaki
AU - Sakakibara, Shotaro
AU - Mizoguchi, Akira
AU - Takai, Yoshimi
AU - Mori, Masahiro
ID - 706
IS - 8
JF - Genes to Cells
SN - 13569597
TI - Roles of afadin in functional differentiations of hippocampal mossy fiber synapse
VL - 22
ER -
TY - JOUR
AB - We answer a question of M. Gromov on the waist of the unit ball.
AU - Akopyan, Arseniy
AU - Karasev, Roman
ID - 707
IS - 4
JF - Bulletin of the London Mathematical Society
SN - 00246093
TI - A tight estimate for the waist of the ball
VL - 49
ER -
TY - JOUR
AB - In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs. Furthermore, we show that stimulation of the corpus callosum at different frequencies in vivo affects proliferation and differentiation of OPCs in a dissimilar way. Our findings suggest that neurons do not influence OPCs in “all-or-none” fashion but use their firing pattern to tune the response and behavior of these nonneuronal cells.
AU - Nagy, Balint
AU - Hovhannisyan, Anahit
AU - Barzan, Ruxandra
AU - Chen, Ting
AU - Kukley, Maria
ID - 708
IS - 8
JF - PLoS Biology
SN - 15449173
TI - Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum
VL - 15
ER -
TY - JOUR
AB - Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations.
AU - Sun, Wuping
AU - Li, Chen
AU - Zhang, Yonghong
AU - Jiang, Changyu
AU - Zhai, Ming-Zhu
AU - Zhou, Qian
AU - Xiao, Lizu
AU - Deng, Qiwen
ID - 709
IS - 8
JF - Cell Biology International
SN - 10656995
TI - Gene expression changes of thermo sensitive transient receptor potential channels in obese mice
VL - 41
ER -
TY - CONF
AB - We revisit the problem of estimating entropy of discrete distributions from independent samples, studied recently by Acharya, Orlitsky, Suresh and Tyagi (SODA 2015), improving their upper and lower bounds on the necessary sample size n. For estimating Renyi entropy of order alpha, up to constant accuracy and error probability, we show the following * Upper bounds n = O(1) 2^{(1-1/alpha)H_alpha} for integer alpha>1, as the worst case over distributions with Renyi entropy equal to H_alpha. * Lower bounds n = Omega(1) K^{1-1/alpha} for any real alpha>1, with the constant being an inverse polynomial of the accuracy, as the worst case over all distributions on K elements. Our upper bounds essentially replace the alphabet size by a factor exponential in the entropy, which offers improvements especially in low or medium entropy regimes (interesting for example in anomaly detection). As for the lower bounds, our proof explicitly shows how the complexity depends on both alphabet and accuracy, partially solving the open problem posted in previous works. The argument for upper bounds derives a clean identity for the variance of falling-power sum of a multinomial distribution. Our approach for lower bounds utilizes convex optimization to find a distribution with possibly worse estimation performance, and may be of independent interest as a tool to work with Le Cam’s two point method.
AU - Obremski, Maciej
AU - Skórski, Maciej
ID - 710
SN - 18688969
TI - Renyi entropy estimation revisited
VL - 81
ER -
TY - CONF
AB - Nested weighted automata (NWA) present a robust and convenient automata-theoretic formalism for quantitative specifications. Previous works have considered NWA that processed input words only in the forward direction. It is natural to allow the automata to process input words backwards as well, for example, to measure the maximal or average time between a response and the preceding request. We therefore introduce and study bidirectional NWA that can process input words in both directions. First, we show that bidirectional NWA can express interesting quantitative properties that are not expressible by forward-only NWA. Second, for the fundamental decision problems of emptiness and universality, we establish decidability and complexity results for the new framework which match the best-known results for the special case of forward-only NWA. Thus, for NWA, the increased expressiveness of bidirectionality is achieved at no additional computational complexity. This is in stark contrast to the unweighted case, where bidirectional finite automata are no more expressive but exponentially more succinct than their forward-only counterparts.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 711
SN - 18688969
TI - Bidirectional nested weighted automata
VL - 85
ER -
TY - JOUR
AB - We establish a weak–strong uniqueness principle for solutions to entropy-dissipating reaction–diffusion equations: As long as a strong solution to the reaction–diffusion equation exists, any weak solution and even any renormalized solution must coincide with this strong solution. Our assumptions on the reaction rates are just the entropy condition and local Lipschitz continuity; in particular, we do not impose any growth restrictions on the reaction rates. Therefore, our result applies to any single reversible reaction with mass-action kinetics as well as to systems of reversible reactions with mass-action kinetics satisfying the detailed balance condition. Renormalized solutions are known to exist globally in time for reaction–diffusion equations with entropy-dissipating reaction rates; in contrast, the global-in-time existence of weak solutions is in general still an open problem–even for smooth data–, thereby motivating the study of renormalized solutions. The key ingredient of our result is a careful adjustment of the usual relative entropy functional, whose evolution cannot be controlled properly for weak solutions or renormalized solutions.
AU - Fischer, Julian L
ID - 712
JF - Nonlinear Analysis: Theory, Methods and Applications
SN - 0362546X
TI - Weak–strong uniqueness of solutions to entropy dissipating reaction–diffusion equations
VL - 159
ER -
TY - JOUR
AB - To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.
AU - Andergassen, Daniel
AU - Dotter, Christoph
AU - Wenzel, Dyniel
AU - Sigl, Verena
AU - Bammer, Philipp
AU - Muckenhuber, Markus
AU - Mayer, Daniela
AU - Kulinski, Tomasz
AU - Theussl, Hans
AU - Penninger, Josef
AU - Bock, Christoph
AU - Barlow, Denise
AU - Pauler, Florian
AU - Hudson, Quanah
ID - 713
JF - eLife
SN - 2050084X
TI - Mapping the mouse Allelome reveals tissue specific regulation of allelic expression
VL - 6
ER -
TY - JOUR
AB - Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.
AU - Brailoiu, Gabriela
AU - Deliu, Elena
AU - Barr, Jeffrey
AU - Console Bram, Linda
AU - Ciuciu, Alexandra
AU - Abood, Mary
AU - Unterwald, Ellen
AU - Brǎiloiu, Eugen
ID - 714
JF - Drug and Alcohol Dependence
SN - 03768716
TI - HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens
VL - 178
ER -
TY - JOUR
AB - We study controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize the expected mean-payoff performance and stability (also known as variability in the literature). We argue that the basic notion of expressing the stability using the statistical variance of the mean payoff is sometimes insufficient, and propose an alternative definition. We show that a strategy ensuring both the expected mean payoff and the variance below given bounds requires randomization and memory, under both the above definitions. We then show that the problem of finding such a strategy can be expressed as a set of constraints.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 1294
JF - Journal of Computer and System Sciences
TI - Trading performance for stability in Markov decision processes
VL - 84
ER -
TY - JOUR
AB - Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.
AU - Paixao, Tiago
AU - Pérez Heredia, Jorge
AU - Sudholt, Dirk
AU - Trubenova, Barbora
ID - 1336
IS - 2
JF - Algorithmica
SN - 01784617
TI - Towards a runtime comparison of natural and artificial evolution
VL - 78
ER -
TY - JOUR
AB - We consider the local eigenvalue distribution of large self-adjoint N×N random matrices H=H∗ with centered independent entries. In contrast to previous works the matrix of variances sij=\mathbbmE|hij|2 is not assumed to be stochastic. Hence the density of states is not the Wigner semicircle law. Its possible shapes are described in the companion paper (Ajanki et al. in Quadratic Vector Equations on the Complex Upper Half Plane. arXiv:1506.05095). We show that as N grows, the resolvent, G(z)=(H−z)−1, converges to a diagonal matrix, diag(m(z)), where m(z)=(m1(z),…,mN(z)) solves the vector equation −1/mi(z)=z+∑jsijmj(z) that has been analyzed in Ajanki et al. (Quadratic Vector Equations on the Complex Upper Half Plane. arXiv:1506.05095). We prove a local law down to the smallest spectral resolution scale, and bulk universality for both real symmetric and complex hermitian symmetry classes.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 1337
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Universality for general Wigner-type matrices
VL - 169
ER -
TY - JOUR
AB - We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of sequences produced under a non-preemptive scheduler. We guarantee that our synthesis does not introduce deadlocks and that the synchronization inserted is optimal w.r.t. a given objective function. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and generation of a set of global constraints over synchronization placements. Each model of the global constraints set corresponds to a correctness-ensuring synchronization placement. The placement that is optimal w.r.t. the given objective function is chosen as the synchronization solution. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient. The implicit specification helped us find one concurrency bug previously missed when model-checking using an explicit, user-provided specification. We implemented objective functions for coarse-grained and fine-grained locking and observed that different synchronization placements are produced for our experiments, favoring a minimal number of synchronization operations or maximum concurrency, respectively.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1338
IS - 2-3
JF - Formal Methods in System Design
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 50
ER -
TY - JOUR
AB - The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.
AU - Giacobbe, Mirco
AU - Guet, Calin C
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Paixao, Tiago
AU - Petrov, Tatjana
ID - 1351
IS - 8
JF - Acta Informatica
SN - 00015903
TI - Model checking the evolution of gene regulatory networks
VL - 54
ER -
TY - JOUR
AB - One of the major challenges in physically based modelling is making simulations efficient. Adaptive models provide an essential solution to these efficiency goals. These models are able to self-adapt in space and time, attempting to provide the best possible compromise between accuracy and speed. This survey reviews the adaptive solutions proposed so far in computer graphics. Models are classified according to the strategy they use for adaptation, from time-stepping and freezing techniques to geometric adaptivity in the form of structured grids, meshes and particles. Applications range from fluids, through deformable bodies, to articulated solids.
AU - Manteaux, Pierre
AU - Wojtan, Christopher J
AU - Narain, Rahul
AU - Redon, Stéphane
AU - Faure, François
AU - Cani, Marie
ID - 1367
IS - 6
JF - Computer Graphics Forum
SN - 01677055
TI - Adaptive physically based models in computer graphics
VL - 36
ER -
TY - JOUR
AB - We consider the problem of computing the set of initial states of a dynamical system such that there exists a control strategy to ensure that the trajectories satisfy a temporal logic specification with probability 1 (almost-surely). We focus on discrete-time, stochastic linear dynamics and specifications given as formulas of the Generalized Reactivity(1) fragment of Linear Temporal Logic over linear predicates in the states of the system. We propose a solution based on iterative abstraction-refinement, and turn-based 2-player probabilistic games. While the theoretical guarantee of our algorithm after any finite number of iterations is only a partial solution, we show that if our algorithm terminates, then the result is the set of all satisfying initial states. Moreover, for any (partial) solution our algorithm synthesizes witness control strategies to ensure almost-sure satisfaction of the temporal logic specification. While the proposed algorithm guarantees progress and soundness in every iteration, it is computationally demanding. We offer an alternative, more efficient solution for the reachability properties that decomposes the problem into a series of smaller problems of the same type. All algorithms are demonstrated on an illustrative case study.
AU - Svoreňová, Mária
AU - Kretinsky, Jan
AU - Chmelik, Martin
AU - Chatterjee, Krishnendu
AU - Cěrná, Ivana
AU - Belta, Cǎlin
ID - 1407
IS - 2
JF - Nonlinear Analysis: Hybrid Systems
TI - Temporal logic control for stochastic linear systems using abstraction refinement of probabilistic games
VL - 23
ER -
TY - JOUR
AB - Phat is an open-source C. ++ library for the computation of persistent homology by matrix reduction, targeted towards developers of software for topological data analysis. We aim for a simple generic design that decouples algorithms from data structures without sacrificing efficiency or user-friendliness. We provide numerous different reduction strategies as well as data types to store and manipulate the boundary matrix. We compare the different combinations through extensive experimental evaluation and identify optimization techniques that work well in practical situations. We also compare our software with various other publicly available libraries for persistent homology.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
AU - Wagner, Hubert
ID - 1433
JF - Journal of Symbolic Computation
SN - 07477171
TI - Phat - Persistent homology algorithms toolbox
VL - 78
ER -
TY - JOUR
AB - We consider N×N Hermitian random matrices H consisting of blocks of size M≥N6/7. The matrix elements are i.i.d. within the blocks, close to a Gaussian in the four moment matching sense, but their distribution varies from block to block to form a block-band structure, with an essential band width M. We show that the entries of the Green’s function G(z)=(H−z)−1 satisfy the local semicircle law with spectral parameter z=E+iη down to the real axis for any η≫N−1, using a combination of the supersymmetry method inspired by Shcherbina (J Stat Phys 155(3): 466–499, 2014) and the Green’s function comparison strategy. Previous estimates were valid only for η≫M−1. The new estimate also implies that the eigenvectors in the middle of the spectrum are fully delocalized.
AU - Bao, Zhigang
AU - Erdös, László
ID - 1528
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Delocalization for a class of random block band matrices
VL - 167
ER -
TY - CONF
AB - We study probabilistic models of natural images and extend the autoregressive family of PixelCNN models by incorporating latent variables. Subsequently, we describe two new generative image models that exploit different image transformations as latent variables: a quantized grayscale view of the image or a multi-resolution image pyramid. The proposed models tackle two known shortcomings of existing PixelCNN models: 1) their tendency to focus on low-level image details, while largely ignoring high-level image information, such as object shapes, and 2) their computationally costly procedure for image sampling. We experimentally demonstrate benefits of our LatentPixelCNN models, in particular showing that they produce much more realistically looking image samples than previous state-of-the-art probabilistic models.
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 1000
SN - 978-151085514-4
TI - PixelCNN models with auxiliary variables for natural image modeling
VL - 70
ER -
TY - CONF
AB - We present a computational approach for designing CurveUps, curvy shells that form from an initially flat state. They consist of small rigid tiles that are tightly held together by two pre-stretched elastic sheets attached to them. Our method allows the realization of smooth, doubly curved surfaces that can be fabricated as a flat piece. Once released, the restoring forces of the pre-stretched sheets support the object to take shape in 3D. CurveUps are structurally stable in their target configuration. The design process starts with a target surface. Our method generates a tile layout in 2D and optimizes the distribution, shape, and attachment areas of the tiles to obtain a configuration that is fabricable and in which the curved up state closely matches the target. Our approach is based on an efficient approximate model and a local optimization strategy for an otherwise intractable nonlinear optimization problem. We demonstrate the effectiveness of our approach for a wide range of shapes, all realized as physical prototypes.
AU - Guseinov, Ruslan
AU - Miguel, Eder
AU - Bickel, Bernd
ID - 1001
IS - 4
TI - CurveUps: Shaping objects from flat plates with tension-actuated curvature
VL - 36
ER -
TY - CONF
AB - We present an interactive design system to create functional mechanical objects. Our computational approach allows novice users to retarget an existing mechanical template to a user-specified input shape. Our proposed representation for a mechanical template encodes a parameterized mechanism, mechanical constraints that ensure a physically valid configuration, spatial relationships of mechanical parts to the user-provided shape, and functional constraints that specify an intended functionality. We provide an intuitive interface and optimization-in-the-loop approach for finding a valid configuration of the mechanism and the shape to ensure that higher-level functional goals are met. Our algorithm interactively optimizes the mechanism while the user manipulates the placement of mechanical components and the shape. Our system allows users to efficiently explore various design choices and to synthesize customized mechanical objects that can be fabricated with rapid prototyping technologies. We demonstrate the efficacy of our approach by retargeting various mechanical templates to different shapes and fabricating the resulting functional mechanical objects.
AU - Zhang, Ran
AU - Auzinger, Thomas
AU - Ceylan, Duygu
AU - Li, Wilmot
AU - Bickel, Bernd
ID - 1002
IS - 4
SN - 07300301
TI - Functionality-aware retargeting of mechanisms to 3D shapes
VL - 36
ER -
TY - CONF
AB - Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an overapproximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. Our experimental results demonstrate the efficiency of the methodology.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 1003
SN - 10450823
TI - An abstraction-refinement methodology for reasoning about network games
ER -
TY - JOUR
AB - The fundamental tasks of the root system are, besides anchoring, mediating interactions between plant and soil and providing the plant with water and nutrients. The architecture of the root system is controlled by endogenous mechanisms that constantly integrate environmental signals, such as availability of nutrients and water. Extremely important for efficient soil exploitation and survival under less favorable conditions is the developmental flexibility of the root system that is largely determined by its postembryonic branching capacity. Modulation of initiation and outgrowth of lateral roots provides roots with an exceptional plasticity, allows optimal adjustment to underground heterogeneity, and enables effective soil exploitation and use of resources. Here we discuss recent advances in understanding the molecular mechanisms that shape the plant root system and integrate external cues to adapt to the changing environment.
AU - Ötvös, Krisztina
AU - Benková, Eva
ID - 1004
JF - Current Opinion in Genetics & Development
SN - 0959437X
TI - Spatiotemporal mechanisms of root branching
VL - 45
ER -
TY - JOUR
AB - Background: The phenomenon of immune priming, i.e. enhanced protection following a secondary exposure to a pathogen, has now been demonstrated in a wide range of invertebrate species. Despite accumulating phenotypic evidence, knowledge of its mechanistic underpinnings is currently very limited. Here we used the system of the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus thuringiensis (Bt) to further our molecular understanding of the oral immune priming phenomenon. We addressed how ingestion of bacterial cues (derived from spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects gene expression upon later challenge exposure, using a whole-transcriptome sequencing approach. Results: Whereas gene expression of individuals primed with the orally non-pathogenic strain showed minor changes to controls, we found that priming with the pathogenic strain induced regulation of a large set of distinct genes, many of which are known immune candidates. Intriguingly, the immune repertoire activated upon priming and subsequent challenge qualitatively differed from the one mounted upon infection with Bt without previous priming. Moreover, a large subset of priming-specific genes showed an inverse regulation compared to their regulation upon challenge only. Conclusions: Our data demonstrate that gene expression upon infection is strongly affected by previous immune priming. We hypothesise that this shift in gene expression indicates activation of a more targeted and efficient response towards a previously encountered pathogen, in anticipation of potential secondary encounter.
AU - Greenwood, Jenny
AU - Milutinovic, Barbara
AU - Peuß, Robert
AU - Behrens, Sarah
AU - Essar, Daniela
AU - Rosenstiel, Philip
AU - Schulenburg, Hinrich
AU - Kurtz, Joachim
ID - 1006
IS - 1
JF - BMC Genomics
SN - 14712164
TI - Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae
VL - 18
ER -
TY - JOUR
AB - A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.
AU - Lang, Moritz
AU - Sontag, Eduardo
ID - 1007
JF - Automatica
SN - 00051098
TI - Zeros of nonlinear systems with input invariances
VL - 81C
ER -
TY - CONF
AB - A standard objective in partially-observable Markov decision processes (POMDPs) is to find a policy that maximizes the expected discounted-sum payoff. However, such policies may still permit unlikely but highly undesirable outcomes, which is problematic especially in safety-critical applications. Recently, there has been a surge of interest in POMDPs where the goal is to maximize the probability to ensure that the payoff is at least a given threshold, but these approaches do not consider any optimization beyond satisfying this threshold constraint. In this work we go beyond both the “expectation” and “threshold” approaches and consider a “guaranteed payoff optimization (GPO)” problem for POMDPs, where we are given a threshold t and the objective is to find a policy σ such that a) each possible outcome of σ yields a discounted-sum payoff of at least t, and b) the expected discounted-sum payoff of σ is optimal (or near-optimal) among all policies satisfying a). We present a practical approach to tackle the GPO problem and evaluate it on standard POMDP benchmarks.
AU - Chatterjee, Krishnendu
AU - Novotny, Petr
AU - Pérez, Guillermo
AU - Raskin, Jean
AU - Zikelic, Djordje
ID - 1009
T2 - Proceedings of the 31st AAAI Conference on Artificial Intelligence
TI - Optimizing expectation with guarantees in POMDPs
VL - 5
ER -
TY - JOUR
AB - We prove a local law in the bulk of the spectrum for random Gram matrices XX∗, a generalization of sample covariance matrices, where X is a large matrix with independent, centered entries with arbitrary variances. The limiting eigenvalue density that generalizes the Marchenko-Pastur law is determined by solving a system of nonlinear equations. Our entrywise and averaged local laws are on the optimal scale with the optimal error bounds. They hold both in the square case (hard edge) and in the properly rectangular case (soft edge). In the latter case we also establish a macroscopic gap away from zero in the spectrum of XX∗.
AU - Alt, Johannes
AU - Erdös, László
AU - Krüger, Torben H
ID - 1010
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for random Gram matrices
VL - 22
ER -
TY - CONF
AB - Pushdown systems (PDSs) and recursive state machines (RSMs), which are linearly equivalent, are standard models for interprocedural analysis. Yet RSMs are more convenient as they (a) explicitly model function calls and returns, and (b) specify many natural parameters for algorithmic analysis, e.g., the number of entries and exits. We consider a general framework where RSM transitions are labeled from a semiring and path properties are algebraic with semiring operations, which can model, e.g., interprocedural reachability and dataflow analysis problems. Our main contributions are new algorithms for several fundamental problems. As compared to a direct translation of RSMs to PDSs and the best-known existing bounds of PDSs, our analysis algorithm improves the complexity for finite-height semirings (that subsumes reachability and standard dataflow properties). We further consider the problem of extracting distance values from the representation structures computed by our algorithm, and give efficient algorithms that distinguish the complexity of a one-time preprocessing from the complexity of each individual query. Another advantage of our algorithm is that our improvements carry over to the concurrent setting, where we improve the bestknown complexity for the context-bounded analysis of concurrent RSMs. Finally, we provide a prototype implementation that gives a significant speed-up on several benchmarks from the SLAM/SDV project.
AU - Chatterjee, Krishnendu
AU - Kragl, Bernhard
AU - Mishra, Samarth
AU - Pavlogiannis, Andreas
ED - Yang, Hongseok
ID - 1011
SN - 03029743
TI - Faster algorithms for weighted recursive state machines
VL - 10201
ER -
TY - JOUR
AB - From microwave ovens to satellite television to the GPS and data services on our mobile phones, microwave technology is everywhere today. But one technology that has so far failed to prove its worth in this wavelength regime is quantum communication that uses the states of single photons as information carriers. This is because single microwave photons, as opposed to classical microwave signals, are extremely vulnerable to noise from thermal excitations in the channels through which they travel. Two new independent studies, one by Ze-Liang Xiang at Technische Universität Wien (Vienna), Austria, and colleagues [1] and another by Benoît Vermersch at the University of Innsbruck, also in Austria, and colleagues [2] now describe a theoretical protocol for microwave quantum communication that is resilient to thermal and other types of noise. Their approach could become a powerful technique to establish fast links between superconducting data processors in a future all-microwave quantum network.
AU - Fink, Johannes M
ID - 1013
IS - 32
JF - Physics
TI - Viewpoint: Microwave quantum states beat the heat
VL - 10
ER -
TY - JOUR
AB - Vortices are commonly observed in the context of classical hydrodynamics: from whirlpools after stirring the coffee in a cup to a violent atmospheric phenomenon such as a tornado, all classical vortices are characterized by an arbitrary circulation value of the local velocity field. On the other hand the appearance of vortices with quantized circulation represents one of the fundamental signatures of macroscopic quantum phenomena. In two-dimensional superfluids quantized vortices play a key role in determining finite-temperature properties, as the superfluid phase and the normal state are separated by a vortex unbinding transition, the Berezinskii-Kosterlitz-Thouless transition. Very recent experiments with two-dimensional superfluid fermions motivate the present work: we present theoretical results based on the renormalization group showing that the universal jump of the superfluid density and the critical temperature crucially depend on the interaction strength, providing a strong benchmark for forthcoming investigations.
AU - Bighin, Giacomo
AU - Salasnich, Luca
ID - 1015
JF - Scientific Reports
SN - 20452322
TI - Vortices and antivortices in two-dimensional ultracold Fermi gases
VL - 7
ER -
TY - JOUR
AB - The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects.
AU - Breuss, Martin
AU - Nguyen, Thai
AU - Srivatsan, Anjana
AU - Leca, Ines
AU - Tian, Guoling
AU - Fritz, Tanja
AU - Hansen, Andi H
AU - Musaev, Damir
AU - Mcevoy Venneri, Jennifer
AU - Kiely, James
AU - Rosti, Rasim
AU - Scott, Eric
AU - Tan, Uner
AU - Kolodner, Richard
AU - Cowan, Nicholas
AU - Keays, David
AU - Gleeson, Joseph
ID - 1016
IS - 2
JF - Human Molecular Genetics
SN - 09646906
TI - Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability
VL - 26
ER -
TY - JOUR
AB - The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot.
AU - Breuss, Martin
AU - Leca, Ines
AU - Gstrein, Thomas
AU - Hansen, Andi H
AU - Keays, David
ID - 1017
JF - Molecular and Cellular Neuroscience
SN - 10447431
TI - Tubulins and brain development: The origins of functional specification
VL - 84
ER -
TY - JOUR
AB - In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The crosstalk between cytokinin response and light is known for a long time. However, the molecular mechanism underlying the interactionbetween light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL (LPH) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT-1 (CKI1), encoding the constitutively active sensor histidine kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE 1 (HY1) which encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertiblephytochromes. Our analysis confirmed the light-dependent regulation oftheCKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors PHYTOCHROME INTERACTING FACTOR 3 (PIF3) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Changes in CKI1 expression observed in lph/hy1-7 and phy mutants correlatewithmisregulation of MSP signaling, changedcytokinin sensitivity and developmental aberrations,previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development.
AU - Dobisova, Tereza
AU - Hrdinova, Vendula
AU - Cuesta, Candela
AU - Michlickova, Sarka
AU - Urbankova, Ivana
AU - Hejatkova, Romana
AU - Zadnikova, Petra
AU - Pernisová, Markéta
AU - Benková, Eva
AU - Hejátko, Jan
ID - 1018
IS - 1
JF - Plant Physiology
TI - Light regulated expression of sensor histidine kinase CKI1 controls cytokinin related development
VL - 174
ER -
TY - JOUR
AB - As a consequence of its difference in copy number between males and females, the X chromosome is subject to unique evolutionary forces and gene regulatory mechanisms. Previous studies of Drosophila melanogaster have shown that the expression of X-linked, testis-specific reporter genes is suppressed in the male germline. However, it is not known whether this phenomenon is restricted to testis-expressed genes or if it is a more general property of genes with tissue-specific expression, which are also underrepresented on the X chromosome. To test this, we compared the expression of three tissue-specific reporter genes (ovary, accessory gland and Malpighian tubule) inserted at various autosomal and X-chromosomal locations. In contrast to testis-specific reporter genes, we found no reduction of X-linked expression in any of the other tissues. In accessory gland and Malpighian tubule, we detected higher expression of the X-linked reporter genes, which suggests that they are at least partially dosage compensated. We found no difference in the tissue-specificity of X-linked and autosomal reporter genes. These findings indicate that, in general, the X chromosome is not a detrimental environment for tissue-specific gene expression and that the suppression of X-linked expression is limited to the male germline.
AU - Argyridou, Eliza
AU - Huylmans, Ann K
AU - Königer, Annabella
AU - Parsch, John
ID - 1019
IS - 1
JF - Heredity
SN - 0018067X
TI - X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster
VL - 119
ER -
TY - JOUR
AB - Cellulose is the most abundant biopolymer on Earth. Cellulose fibers, such as the one extracted form cotton or woodpulp, have been used by humankind for hundreds of years to make textiles and paper. Here we show how, by engineering light-matter interaction, we can optimize light scattering using exclusively cellulose nanocrystals. The produced material is sustainable, biocompatible, and when compared to ordinary microfiber-based paper, it shows enhanced scattering strength (×4), yielding a transport mean free path as low as 3.5 μm in the visible light range. The experimental results are in a good agreement with the theoretical predictions obtained with a diffusive model for light propagation.
AU - Caixeiro, Soraya
AU - Peruzzo, Matilda
AU - Onelli, Olimpia
AU - Vignolini, Silvia
AU - Sapienza, Riccardo
ID - 1020
IS - 9
JF - ACS Applied Materials and Interfaces
SN - 19448244
TI - Disordered cellulose based nanostructures for enhanced light scattering
VL - 9
ER -
TY - JOUR
AB - Most flows in nature and engineering are turbulent because of their large velocities and spatial scales. Laboratory experiments on rotating quasi-Keplerian flows, for which the angular velocity decreases radially but the angular momentum increases, are however laminar at Reynolds numbers exceeding one million. This is in apparent contradiction to direct numerical simulations showing that in these experiments turbulence transition is triggered by the axial boundaries. We here show numerically that as the Reynolds number increases, turbulence becomes progressively confined to the boundary layers and the flow in the bulk fully relaminarizes. Our findings support that turbulence is unlikely to occur in isothermal constant-density quasi-Keplerian flows.
AU - Lopez Alonso, Jose M
AU - Avila, Marc
ID - 1021
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Boundary layer turbulence in experiments on quasi Keplerian flows
VL - 817
ER -
TY - JOUR
AB - We introduce a multiscale topological description of the Megaparsec web-like cosmic matter distribution. Betti numbers and topological persistence offer a powerful means of describing the rich connectivity structure of the cosmic web and of its multiscale arrangement of matter and galaxies. Emanating from algebraic topology and Morse theory, Betti numbers and persistence diagrams represent an extension and deepening of the cosmologically familiar topological genus measure and the related geometric Minkowski functionals. In addition to a description of the mathematical background, this study presents the computational procedure for computing Betti numbers and persistence diagrams for density field filtrations. The field may be computed starting from a discrete spatial distribution of galaxies or simulation particles. The main emphasis of this study concerns an extensive and systematic exploration of the imprint of different web-like morphologies and different levels of multiscale clustering in the corresponding computed Betti numbers and persistence diagrams. To this end, we use Voronoi clustering models as templates for a rich variety of web-like configurations and the fractal-like Soneira-Peebles models exemplify a range of multiscale configurations. We have identified the clear imprint of cluster nodes, filaments, walls, and voids in persistence diagrams, along with that of the nested hierarchy of structures in multiscale point distributions. We conclude by outlining the potential of persistent topology for understanding the connectivity structure of the cosmic web, in large simulations of cosmic structure formation and in the challenging context of the observed galaxy distribution in large galaxy surveys.
AU - Pranav, Pratyush
AU - Edelsbrunner, Herbert
AU - Van De Weygaert, Rien
AU - Vegter, Gert
AU - Kerber, Michael
AU - Jones, Bernard
AU - Wintraecken, Mathijs
ID - 1022
IS - 4
JF - Monthly Notices of the Royal Astronomical Society
SN - 00358711
TI - The topology of the cosmic web in terms of persistent Betti numbers
VL - 465
ER -
TY - JOUR
AB - We consider products of independent square non-Hermitian random matrices. More precisely, let X1,…, Xn be independent N × N random matrices with independent entries (real or complex with independent real and imaginary parts) with zero mean and variance 1/N. Soshnikov-O’Rourke [19] and Götze-Tikhomirov [15] showed that the empirical spectral distribution of the product of n random matrices with iid entries converges to (equation found). We prove that if the entries of the matrices X1,…, Xn are independent (but not necessarily identically distributed) and satisfy uniform subexponential decay condition, then in the bulk the convergence of the ESD of X1,…, Xn to (0.1) holds up to the scale N–1/2+ε.
AU - Nemish, Yuriy
ID - 1023
JF - Electronic Journal of Probability
SN - 10836489
TI - Local law for the product of independent non-Hermitian random matrices with independent entries
VL - 22
ER -
TY - JOUR
AB - Many organ surfaces are covered by a protective epithelial-cell layer. It emerges that such layers are maintained by cell stretching that triggers cell division mediated by the force-sensitive ion-channel protein Piezo1. See Letter p.118
AU - Heisenberg, Carl-Philipp J
ID - 1025
IS - 7643
JF - Nature
SN - 00280836
TI - Cell biology: Stretched divisions
VL - 543
ER -
TY - JOUR
AB - The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.
AU - Agus, Viviana
AU - Janovjak, Harald L
ID - 1026
JF - Current Opinion in Biotechnology
SN - 09581669
TI - Optogenetic methods in drug screening: Technologies and applications
VL - 48
ER -
TY - JOUR
AB - Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.
AU - Kainrath, Stephanie
AU - Stadler, Manuela
AU - Gschaider-Reichhart, Eva
AU - Distel, Martin
AU - Janovjak, Harald L
ID - 1028
IS - 16
JF - Angewandte Chemie - International Edition
SN - 14337851
TI - Green-light-induced inactivation of receptor signaling using cobalamin-binding domains
VL - 56
ER -
TY - JOUR
AB - Auf der Suche nach einem Bibliothekssystem entschied sich die Forschungseinrichtung IST Austria im Jahr 2014 für das Open-Source-Produkt Koha. In einem ersten Schritt wurden zunächst Grundfunktionen aktiviert um im Anschluss diverse zusätzliche Tools zum Einsatz zu bringen. Die große Flexibilität des Systems erlaubt maßgeschneiderte Lösungen für unterschiedlichste Institutionen. Trotz Herausforderungen kann die Bibliothek auf eine erfolgreiche Implementierung zurückblicken.
AU - Villányi, Márton
ID - 1030
IS - 1
JF - Informationspraxis
SN - 2297-3249
TI - Ein freies Bibliothekssystem für wissenschaftliche Bibliotheken – Werkstattbericht der IST Austria Library
VL - 3
ER -
TY - JOUR
AB - Severe environmental change can drive a population extinct unless the population adapts in time to the new conditions (“evolutionary rescue”). How does biparental sexual reproduction influence the chances of population persistence compared to clonal reproduction or selfing? In this article, we set up a one‐locus two‐allele model for adaptation in diploid species, where rescue is contingent on the establishment of the mutant homozygote. Reproduction can occur by random mating, selfing, or clonally. Random mating generates and destroys the rescue mutant; selfing is efficient at generating it but at the same time depletes the heterozygote, which can lead to a low mutant frequency in the standing genetic variation. Due to these (and other) antagonistic effects, we find a nontrivial dependence of population survival on the rate of sex/selfing, which is strongly influenced by the dominance coefficient of the mutation before and after the environmental change. Importantly, since mating with the wild‐type breaks the mutant homozygote up, a slow decay of the wild‐type population size can impede rescue in randomly mating populations.
AU - Uecker, Hildegard
ID - 1063
IS - 4
JF - Evolution
SN - 00143820
TI - Evolutionary rescue in randomly mating, selfing, and clonal populations
VL - 71
ER -
TY - JOUR
AB - We consider the problem of reachability in pushdown graphs. We study the problem for pushdown graphs with constant treewidth. Even for pushdown graphs with treewidth 1, for the reachability problem we establish the following: (i) the problem is PTIME-complete, and (ii) any subcubic algorithm for the problem would contradict the k-clique conjecture and imply faster combinatorial algorithms for cliques in graphs.
AU - Chatterjee, Krishnendu
AU - Osang, Georg F
ID - 1065
JF - Information Processing Letters
SN - 00200190
TI - Pushdown reachability with constant treewidth
VL - 122
ER -
TY - JOUR
AB - Simulation is an attractive alternative to language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. While fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable in general, whereas the (quantitative) simulation reduces to quantitative games, which admit pseudo-polynomial time algorithms.
In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games, yet they still admit pseudo-polynomial time algorithms.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Velner, Yaron
ID - 1066
IS - 2
JF - Information and Computation
TI - Quantitative fair simulation games
VL - 254
ER -
TY - JOUR
AB - Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during “doming,” when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.
AU - Morita, Hitoshi
AU - Grigolon, Silvia
AU - Bock, Martin
AU - Krens, Gabriel
AU - Salbreux, Guillaume
AU - Heisenberg, Carl-Philipp J
ID - 1067
IS - 4
JF - Developmental Cell
SN - 15345807
TI - The physical basis of coordinated tissue spreading in zebrafish gastrulation
VL - 40
ER -
TY - JOUR
AB - Given a finite set of points in Rn and a radius parameter, we study the Čech, Delaunay–Čech, Delaunay (or alpha), and Wrap complexes in the light of generalized discrete Morse theory. Establishing the Čech and Delaunay complexes as sublevel sets of generalized discrete Morse functions, we prove that the four complexes are simple-homotopy equivalent by a sequence of simplicial collapses, which are explicitly described by a single discrete gradient field.
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 1072
IS - 5
JF - Transactions of the American Mathematical Society
TI - The Morse theory of Čech and delaunay complexes
VL - 369
ER -
TY - JOUR
AB - Let X and Y be finite simplicial sets (e.g. finite simplicial complexes), both equipped with a free simplicial action of a finite group G. Assuming that Y is d-connected and dimX≤2d, for some d≥1, we provide an algorithm that computes the set of all equivariant homotopy classes of equivariant continuous maps |X|→|Y|; the existence of such a map can be decided even for dimX≤2d+1. This yields the first algorithm for deciding topological embeddability of a k-dimensional finite simplicial complex into Rn under the condition k≤23n−1. More generally, we present an algorithm that, given a lifting-extension problem satisfying an appropriate stability assumption, computes the set of all homotopy classes of solutions. This result is new even in the non-equivariant situation.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Vokřínek, Lukáš
ID - 1073
IS - 4
JF - Discrete & Computational Geometry
SN - 01795376
TI - Algorithmic solvability of the lifting extension problem
VL - 54
ER -
TY - JOUR
AB - Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.
AU - Ringbauer, Harald
AU - Coop, Graham
AU - Barton, Nicholas H
ID - 1074
IS - 3
JF - Genetics
SN - 00166731
TI - Inferring recent demography from isolation by distance of long shared sequence blocks
VL - 205
ER -
TY - JOUR
AB - Signatures of the Coulomb corrections in the photoelectron momentum distribution during laser-induced ionization of atoms or ions in tunneling and multiphoton regimes are investigated analytically in the case of a one-dimensional problem. A high-order Coulomb-corrected strong-field approximation is applied, where the exact continuum state in the S matrix is approximated by the eikonal Coulomb-Volkov state including the second-order corrections to the eikonal. Although without high-order corrections our theory coincides with the known analytical R-matrix (ARM) theory, we propose a simplified procedure for the matrix element derivation. Rather than matching the eikonal Coulomb-Volkov wave function with the bound state as in the ARM theory to remove the Coulomb singularity, we calculate the matrix element via the saddle-point integration method by time as well as by coordinate, and in this way avoiding the Coulomb singularity. The momentum shift in the photoelectron momentum distribution with respect to the ARM theory due to high-order corrections is analyzed for tunneling and multiphoton regimes. The relation of the quantum corrections to the tunneling delay time is discussed.
AU - Klaiber, Michael
AU - Daněk, Jiří
AU - Yakaboylu, Enderalp
AU - Hatsagortsyan, Karen
AU - Keitel, Christoph
ID - 1076
IS - 2
JF - Physical Review A - Atomic, Molecular, and Optical Physics
SN - 24699926
TI - Strong-field ionization via a high-order Coulomb-corrected strong-field approximation
VL - 95
ER -
TY - JOUR
AB - Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.
AU - Fernandes Redondo, Rodrigo A
AU - Vladar, Harold
AU - Włodarski, Tomasz
AU - Bollback, Jonathan P
ID - 1077
IS - 126
JF - Journal of the Royal Society Interface
SN - 17425689
TI - Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family
VL - 14
ER -
TY - JOUR
AB - One of the key questions in understanding plant development is how single cells behave in a larger context of the tissue. Therefore, it requires the observation of the whole organ with a high spatial- as well as temporal resolution over prolonged periods of time, which may cause photo-toxic effects. This protocol shows a plant sample preparation method for light-sheet microscopy, which is characterized by mounting the plant vertically on the surface of a gel. The plant is mounted in such a way that the roots are submerged in a liquid medium while the leaves remain in the air. In order to ensure photosynthetic activity of the plant, a custom-made lighting system illuminates the leaves. To keep the roots in darkness the water surface is covered with sheets of black plastic foil. This method allows long-term imaging of plant organ development in standardized conditions.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Friml, Jirí
ID - 1078
IS - 119
JF - Journal of visualized experiments JoVE
TI - Light sheet fluorescence microscopy of plant roots growing on the surface of a gel
VL - 2017
ER -
TY - JOUR
AB - We study the ionization problem in the Thomas-Fermi-Dirac-von Weizsäcker theory for atoms and molecules. We prove the nonexistence of minimizers for the energy functional when the number of electrons is large and the total nuclear charge is small. This nonexistence result also applies to external potentials decaying faster than the Coulomb potential. In the case of arbitrary nuclear charges, we obtain the nonexistence of stable minimizers and radial minimizers.
AU - Nam, Phan
AU - Van Den Bosch, Hanne
ID - 1079
IS - 2
JF - Mathematical Physics, Analysis and Geometry
SN - 13850172
TI - Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges
VL - 20
ER -
TY - JOUR
AB - Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods.
AU - Reiter, Johannes
AU - Makohon Moore, Alvin
AU - Gerold, Jeffrey
AU - Božić, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 1080
JF - Nature Communications
SN - 20411723
TI - Reconstructing metastatic seeding patterns of human cancers
VL - 8
ER -
TY - JOUR
AB - BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.
AU - Fang, Chong
AU - Nagy-Staron, Anna A
AU - Grafe, Martin
AU - Heermann, Ralf
AU - Jung, Kirsten
AU - Gebhard, Susanne
AU - Mascher, Thorsten
ID - 1084
IS - 1
JF - Molecular Microbiology
SN - 0950382X
TI - Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis
VL - 104
ER -
TY - JOUR
AB - Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution.
AU - Wright, Alison
AU - Darolti, Iulia
AU - Bloch, Natasha
AU - Oostra, Vicencio
AU - Sandkam, Benjamin
AU - Buechel, Séverine
AU - Kolm, Niclas
AU - Breden, Felix
AU - Vicoso, Beatriz
AU - Mank, Judith
ID - 1085
JF - Nature Communications
SN - 20411723
TI - Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation
VL - 8
ER -
TY - JOUR
AB - Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.
AU - Di Giglio, Maria
AU - Muttenthaler, Markus
AU - Harpsøe, Kasper
AU - Liutkeviciute, Zita
AU - Keov, Peter
AU - Eder, Thomas
AU - Rattei, Thomas
AU - Arrowsmith, Sarah
AU - Wray, Susan
AU - Marek, Ales
AU - Elbert, Tomas
AU - Alewood, Paul
AU - Gloriam, David
AU - Gruber, Christian
ID - 1086
JF - Scientific Reports
TI - Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide
VL - 7
ER -
TY - JOUR
AB - Using extensive direct numerical simulations, the dynamics of laminar-turbulent fronts in pipe flow is investigated for Reynolds numbers between and 5500. We here investigate the physical distinction between the fronts of weak and strong slugs both by analysing the turbulent kinetic energy budget and by comparing the downstream front motion to the advection speed of bulk turbulent structures. Our study shows that weak downstream fronts travel slower than turbulent structures in the bulk and correspond to decaying turbulence at the front. At the downstream front speed becomes faster than the advection speed, marking the onset of strong fronts. In contrast to weak fronts, turbulent eddies are generated at strong fronts by feeding on the downstream laminar flow. Our study also suggests that temporal fluctuations of production and dissipation at the downstream laminar-turbulent front drive the dynamical switches between the two types of front observed up to.
AU - Song, Baofang
AU - Barkley, Dwight
AU - Hof, Björn
AU - Avila, Marc
ID - 1087
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Speed and structure of turbulent fronts in pipe flow
VL - 813
ER -
TY - JOUR
AB - We discuss properties of distributions that are multivariate totally positive of order two (MTP2) related to conditional independence. In particular, we show that any independence model generated by an MTP2 distribution is a compositional semigraphoid which is upward-stable and singleton-transitive. In addition, we prove that any MTP2 distribution satisfying an appropriate support condition is faithful to its concentration graph. Finally, we analyze factorization properties of MTP2 distributions and discuss ways of constructing MTP2 distributions; in particular we give conditions on the log-linear parameters of a discrete distribution which ensure MTP2 and characterize conditional Gaussian distributions which satisfy MTP2.
AU - Fallat, Shaun
AU - Lauritzen, Steffen
AU - Sadeghi, Kayvan
AU - Uhler, Caroline
AU - Wermuth, Nanny
AU - Zwiernik, Piotr
ID - 1089
IS - 3
JF - Annals of Statistics
SN - 00905364
TI - Total positivity in Markov structures
VL - 45
ER -
TY - JOUR
AB - In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems.
AU - Deny, Stephane
AU - Ferrari, Ulisse
AU - Mace, Emilie
AU - Yger, Pierre
AU - Caplette, Romain
AU - Picaud, Serge
AU - Tkacik, Gasper
AU - Marre, Olivier
ID - 1104
IS - 1
JF - Nature Communications
SN - 20411723
TI - Multiplexed computations in retinal ganglion cells of a single type
VL - 8
ER -
TY - CONF
AB - In this work we study the learnability of stochastic processes with respect to the conditional risk, i.e. the existence of a learning algorithm that improves its next-step performance with the amount of observed data. We introduce a notion of pairwise discrepancy between conditional distributions at different times steps and show how certain properties of these discrepancies can be used to construct a successful learning algorithm. Our main results are two theorems that establish criteria for learnability for many classes of stochastic processes, including all special cases studied previously in the literature.
AU - Zimin, Alexander
AU - Lampert, Christoph
ID - 1108
TI - Learning theory for conditional risk minimization
VL - 54
ER -
TY - JOUR
AB - Rotation of molecules embedded in He nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear -- instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its He shell. Our results open novel opportunities for studying non-equilibrium solute-solvent dynamics and quantum thermalization.
AU - Shepperson, Benjamin
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Kaczmarczyk, Jan
AU - Zillich, Robert
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 1109
IS - 20
JF - Physical Review Letters
TI - Laser-induced rotation of iodine molecules in helium nanodroplets: Revivals and breaking-free
VL - 118
ER -
TY - JOUR
AB - The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Flavonols have been shown to alter auxin transport activity and changes in flavonol accumulation in the Arabidopsis thaliana rol1-2 mutant cause defects in auxin transport and seedling development. A new mutation in ROOTS CURL IN NPA 1 (RCN1), encoding a regulatory subunit of the phosphatase PP2A, was found to suppress the growth defects of rol1-2 without changing the flavonol content. rol1-2 rcn1-3 double mutants show wild type-like auxin transport activity while levels of free auxin are not affected by rcn1-3. In the rol1-2 mutant, PIN2 shows a flavonol-induced basal-to-apical shift in polar localization which is reversed in the rol1-2 rcn1-3 to basal localization. In vivo analysis of PINOID action, a kinase known to influence PIN protein localization in a PP2A-antagonistic manner, revealed a negative impact of flavonols on PINOID activity. Together, these data suggest that flavonols affect auxin transport by modifying the antagonistic kinase/phosphatase equilibrium.
AU - Kuhn, Benjamin
AU - Nodzyński, Tomasz
AU - Errafi, Sanae
AU - Bucher, Rahel
AU - Gupta, Shibu
AU - Aryal, Bibek
AU - Dobrev, Petre
AU - Bigler, Laurent
AU - Geisler, Markus
AU - Zažímalová, Eva
AU - Friml, Jirí
AU - Ringli, Christoph
ID - 1110
JF - Scientific Reports
SN - 20452322
TI - Flavonol-induced changes in PIN2 polarity and auxin transport in the Arabidopsis thaliana rol1-2 mutant require phosphatase activity
VL - 7
ER -
TY - JOUR
AB - Adaptation depends critically on the effects of new mutations and their dependency on the genetic background in which they occur. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape. We analyze populations in the weak-mutation regime and characterize the conditions that enable them to quickly reach the fitness peak as a function of the number of sites under selection. We show that for additive landscapes there is a critical selection strength enabling populations to reach high-fitness genotypes, regardless of the distribution of effects. This threshold scales with the number of sites under selection, effectively setting a limit to adaptation, and results from the inevitable increase in deleterious mutational pressure as the population adapts in a space of discrete genotypes. Furthermore, we show that for the class of all unimodal landscapes this condition is sufficient but not necessary for rapid adaptation, as in some highly epistatic landscapes the critical strength does not depend on the number of sites under selection; effectively removing this barrier to adaptation.
AU - Heredia, Jorge
AU - Trubenova, Barbora
AU - Sudholt, Dirk
AU - Paixao, Tiago
ID - 1111
IS - 2
JF - Genetics
SN - 00166731
TI - Selection limits to adaptive walks on correlated landscapes
VL - 205
ER -
TY - CONF
AB - There has been renewed interest in modelling the behaviour of evolutionary algorithms by more traditional mathematical objects, such as ordinary differential equations or Markov chains. The advantage is that the analysis becomes greatly facilitated due to the existence of well established methods. However, this typically comes at the cost of disregarding information about the process. Here, we introduce the use of stochastic differential equations (SDEs) for the study of EAs. SDEs can produce simple analytical results for the dynamics of stochastic processes, unlike Markov chains which can produce rigorous but unwieldy expressions about the dynamics. On the other hand, unlike ordinary differential equations (ODEs), they do not discard information about the stochasticity of the process. We show that these are especially suitable for the analysis of fixed budget scenarios and present analogs of the additive and multiplicative drift theorems for SDEs. We exemplify the use of these methods for two model algorithms ((1+1) EA and RLS) on two canonical problems(OneMax and LeadingOnes).
AU - Paixao, Tiago
AU - Pérez Heredia, Jorge
ID - 1112
SN - 978-145034651-1
T2 - Proceedings of the 14th ACM/SIGEVO Conference on Foundations of Genetic Algorithms
TI - An application of stochastic differential equations to evolutionary algorithms
ER -
TY - JOUR
AB - A drawing of a graph G is radial if the vertices of G are placed on concentric circles C 1 , . . . , C k with common center c , and edges are drawn radially : every edge intersects every circle centered at c at most once. G is radial planar if it has a radial embedding, that is, a crossing-free radial drawing. If the vertices of G are ordered or partitioned into ordered levels (as they are for leveled graphs), we require that the assignment of vertices to circles corresponds to the given ordering or leveling. We show that a graph G is radial planar if G has a radial drawing in which every two edges cross an even number of times; the radial embedding has the same leveling as the radial drawing. In other words, we establish the weak variant of the Hanani-Tutte theorem for radial planarity. This generalizes a result by Pach and Toth.
AU - Fulek, Radoslav
AU - Pelsmajer, Michael
AU - Schaefer, Marcus
ID - 1113
IS - 1
JF - Journal of Graph Algorithms and Applications
TI - Hanani-Tutte for radial planarity
VL - 21
ER -
TY - JOUR
AB - Nonequilibrium phase transitions exist in damped-driven open quantum systems when the continuous tuning of an external parameter leads to a transition between two robust steady states. In second-order transitions this change is abrupt at a critical point, whereas in first-order transitions the two phases can coexist in a critical hysteresis domain. Here, we report the observation of a first-order dissipative quantum phase transition in a driven circuit quantum electrodynamics system. It takes place when the photon blockade of the driven cavity-atom system is broken by increasing the drive power. The observed experimental signature is a bimodal phase space distribution with varying weights controlled by the drive strength. Our measurements show an improved stabilization of the classical attractors up to the millisecond range when the size of the quantum system is increased from one to three artificial atoms. The formation of such robust pointer states could be used for new quantum measurement schemes or to investigate multiphoton phases of finite-size, nonlinear, open quantum systems.
AU - Fink, Johannes M
AU - Dombi, András
AU - Vukics, András
AU - Wallraff, Andreas
AU - Domokos, Peter
ID - 1114
IS - 1
JF - Physical Review X
SN - 21603308
TI - Observation of the photon blockade breakdown phase transition
VL - 7
ER -
TY - CONF
AB - Time-triggered switched networks are a deterministic communication infrastructure used by real-time distributed embedded systems. Due to the criticality of the applications running over them, developers need to ensure that end-to-end communication is dependable and predictable. Traditional approaches assume static networks that are not flexible to changes caused by reconfigurations or, more importantly, faults, which are dealt with in the application using redundancy. We adopt the concept of handling faults in the switches from non-real-time networks while maintaining the required predictability.
We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. For a given network with a forwarding scheme and a constant ℓ, we compute the {\em score} of the scheme, namely the probability (induced by faults) that at least ℓ messages arrive on time. We reduce the scoring problem to a reachability problem on a Markov chain with a "product-like" structure. Its special structure allows us to reason about it symbolically, and reduce the scoring problem to #SAT. Our solution is generic and can be adapted to different networks and other contexts. Also, we show the computational complexity of the scoring problem is #P-complete, and we study methods to estimate the score. We evaluate the effectiveness of our techniques with an implementation.
AU - Avni, Guy
AU - Goel, Shubham
AU - Henzinger, Thomas A
AU - Rodríguez Navas, Guillermo
ID - 1116
SN - 03029743
TI - Computing scores of forwarding schemes in switched networks with probabilistic faults
VL - 10206
ER -
TY - JOUR
AB - GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author
AU - Chen, Chong
AU - Arai, Itaru
AU - Satterield, Rachel
AU - Young, Samuel
AU - Jonas, Peter M
ID - 1117
IS - 3
JF - Cell Reports
SN - 22111247
TI - Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse
VL - 18
ER -
TY - JOUR
AB - Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.
AU - Gan, Jian
AU - Weng, Shih-Ming
AU - Pernia-Andrade, Alejandro
AU - Csicsvari, Jozsef L
AU - Jonas, Peter M
ID - 1118
IS - 2
JF - Neuron
TI - Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo
VL - 93
ER -
TY - JOUR
AB - Understanding the behavior of molecules interacting with superfluid helium represents a formidable challenge and, in general, requires approaches relying on large-scale numerical simulations. Here we demonstrate that experimental data collected over the last 20 years provide evidence that molecules immersed in superfluid helium form recently-predicted angulon quasiparticles [Phys. Rev. Lett. 114, 203001 (2015)]. Most importantly, casting the many-body problem in terms of angulons amounts to a drastic simplification and yields effective molecular moments of inertia as straightforward analytic solutions of a simple microscopic Hamiltonian. The outcome of the angulon theory is in good agreement with experiment for a broad range of molecular impurities, from heavy to medium-mass to light species. These results pave the way to understanding molecular rotation in liquid and crystalline phases in terms of the angulon quasiparticle.
AU - Lemeshko, Mikhail
ID - 1119
IS - 9
JF - Physical Review Letters
SN - 00319007
TI - Quasiparticle approach to molecules interacting with quantum solvents
VL - 118
ER -
TY - JOUR
AB - The existence of a self-localization transition in the polaron problem has been under an active debate ever since Landau suggested it 83 years ago. Here we reveal the self-localization transition for the rotational analogue of the polaron -- the angulon quasiparticle. We show that, unlike for the polarons, self-localization of angulons occurs at finite impurity-bath coupling already at the mean-field level. The transition is accompanied by the spherical-symmetry breaking of the angulon ground state and a discontinuity in the first derivative of the ground-state energy. Moreover, the type of the symmetry breaking is dictated by the symmetry of the microscopic impurity-bath interaction, which leads to a number of distinct self-localized states. The predicted effects can potentially be addressed in experiments on cold molecules trapped in superfluid helium droplets and ultracold quantum gases, as well as on electronic excitations in solids and Bose-Einstein condensates.
AU - Li, Xiang
AU - Seiringer, Robert
AU - Lemeshko, Mikhail
ID - 1120
IS - 3
JF - Physical Review A
SN - 24699926
TI - Angular self-localization of impurities rotating in a bosonic bath
VL - 95
ER -
TY - JOUR
AB - The hippocampus is thought to initiate systems-wide mnemonic processes through the reactivation of previously acquired spatial and episodic memory traces, which can recruit the entorhinal cortex as a first stage of memory redistribution to other brain areas. Hippocampal reactivation occurs during sharp wave-ripples, in which synchronous network firing encodes sequences of places.We investigated the coordination of this replay by recording assembly activity simultaneously in the CA1 region of the hippocampus and superficial layers of the medial entorhinal cortex. We found that entorhinal cell assemblies can replay trajectories independently of the hippocampus and sharp wave-ripples. This suggests that the hippocampus is not the sole initiator of spatial and episodic memory trace reactivation. Memory systems involved in these processes may include nonhierarchical, parallel components.
AU - O'Neill, Joseph
AU - Boccara, Charlotte
AU - Stella, Federico
AU - Schönenberger, Philipp
AU - Csicsvari, Jozsef L
ID - 1132
IS - 6321
JF - Science
SN - 00368075
TI - Superficial layers of the medial entorhinal cortex replay independently of the hippocampus
VL - 355
ER -
TY - JOUR
AB - It is a common knowledge that an effective interaction of a quantum impurity with an electromagnetic field can be screened by surrounding charge carriers, whether mobile or static. Here we demonstrate that very strong, "anomalous" screening can take place in the presence of a neutral, weakly polarizable environment, due to an exchange of orbital angular momentum between the impurity and the bath. Furthermore, we show that it is possible to generalize all phenomena related to isolated impurities in an external field to the case when a many-body environment is present, by casting the problem in terms of the angulon quasiparticle. As a result, the relevant observables such as the effective Rabi frequency, geometric phase, and impurity spatial alignment are straightforward to evaluate in terms of a single parameter: the angular-momentum-dependent screening factor.
AU - Yakaboylu, Enderalp
AU - Lemeshko, Mikhail
ID - 1133
IS - 8
JF - Physical Review Letters
SN - 00319007
TI - Anomalous screening of quantum impurities by a neutral environment
VL - 118
ER -
TY - JOUR
AB - We show that matrix elements of functions of N × N Wigner matrices fluctuate on a scale of order N−1/2 and we identify the limiting fluctuation. Our result holds for any function f of the matrix that has bounded variation thus considerably relaxing the regularity requirement imposed in [7, 11].
AU - Erdös, László
AU - Schröder, Dominik J
ID - 1144
JF - Electronic Communications in Probability
TI - Fluctuations of functions of Wigner matrices
VL - 21
ER -
TY - JOUR
AB - Aim: The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine. Methods: Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N 1-methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N 1-methyl-2-pyridone-5-carboxamide during the test period were examined. Results: The level of 3-h plasma nicotinamide, N 1-methylnicotinamide, homocysteine, the urinary excretion of N 1-methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N 1-methylnicotinamide (1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM group. Conclusion: The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
AU - Sun, Wuping
AU - Zhai, Ming-Zhu
AU - Li, Da
AU - Zhou, Yiming
AU - Chen, Nana
AU - Guo, Ming
AU - Zhou, Shisheng
ID - 1146
IS - 4
JF - Clinical Nutrition
TI - Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels
VL - 36
ER -
TY - JOUR
AB - We propose a new memetic strategy that can solve the multi-physics, complex inverse problems, formulated as the multi-objective optimization ones, in which objectives are misfits between the measured and simulated states of various governing processes. The multi-deme structure of the strategy allows for both, intensive, relatively cheap exploration with a moderate accuracy and more accurate search many regions of Pareto set in parallel. The special type of selection operator prefers the coherent alternative solutions, eliminating artifacts appearing in the particular processes. The additional accuracy increment is obtained by the parallel convex searches applied to the local scalarizations of the misfit vector. The strategy is dedicated for solving ill-conditioned problems, for which inverting the single physical process can lead to the ambiguous results. The skill of the selection in artifact elimination is shown on the benchmark problem, while the whole strategy was applied for identification of oil deposits, where the misfits are related to various frequencies of the magnetic and electric waves of the magnetotelluric measurements. 2016 Elsevier B.V.
AU - Gajda-Zagorska, Ewa P
AU - Schaefer, Robert
AU - Smołka, Maciej
AU - Pardo, David
AU - Alvarez Aramberri, Julen
ID - 1152
JF - Journal of Computational Science
SN - 18777503
TI - A multi objective memetic inverse solver reinforced by local optimization methods
VL - 18
ER -
TY - THES
AB - This dissertation concerns the automatic verification of probabilistic systems and programs with arrays by statistical and logical methods. Although statistical and logical methods are different in nature, we show that they can be successfully combined for system analysis. In the first part of the dissertation we present a new statistical algorithm for the verification of probabilistic systems with respect to unbounded properties, including linear temporal logic. Our algorithm often performs faster than the previous approaches, and at the same time requires less information about the system. In addition, our method can be generalized to unbounded quantitative properties such as mean-payoff bounds. In the second part, we introduce two techniques for comparing probabilistic systems. Probabilistic systems are typically compared using the notion of equivalence, which requires the systems to have the equal probability of all behaviors. However, this notion is often too strict, since probabilities are typically only empirically estimated, and any imprecision may break the relation between processes. On the one hand, we propose to replace the Boolean notion of equivalence by a quantitative distance of similarity. For this purpose, we introduce a statistical framework for estimating distances between Markov chains based on their simulation runs, and we investigate which distances can be approximated in our framework. On the other hand, we propose to compare systems with respect to a new qualitative logic, which expresses that behaviors occur with probability one or a positive probability. This qualitative analysis is robust with respect to modeling errors and applicable to many domains. In the last part, we present a new quantifier-free logic for integer arrays, which allows us to express counting. Counting properties are prevalent in array-manipulating programs, however they cannot be expressed in the quantified fragments of the theory of arrays. We present a decision procedure for our logic, and provide several complexity results.
AU - Daca, Przemyslaw
ID - 1155
TI - Statistical and logical methods for property checking
ER -
TY - JOUR
AB - Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.
AU - Steenackers, Ward
AU - Klíma, Petr
AU - Quareshy, Mussa
AU - Cesarino, Igor
AU - Kumpf, Robert
AU - Corneillie, Sander
AU - Araújo, Pedro
AU - Viaene, Tom
AU - Goeminne, Geert
AU - Nowack, Moritz
AU - Ljung, Karin
AU - Friml, Jirí
AU - Blakeslee, Joshua
AU - Novák, Ondřej
AU - Zažímalová, Eva
AU - Napier, Richard
AU - Boerjan, Wout
AU - Vanholme, Bartel
ID - 1159
IS - 1
JF - Plant Physiology
SN - 00320889
TI - Cis-cinnamic acid is a novel natural auxin efflux inhibitor that promotes lateral root formation
VL - 173
ER -
TY - JOUR
AB - We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field.
AU - Altmeyer, Sebastian
AU - Do, Younghae
AU - Lai, Ying
ID - 1160
JF - Scientific Reports
SN - 20452322
TI - Dynamics of ferrofluidic flow in the Taylor-Couette system with a small aspect ratio
VL - 7
ER -
TY - JOUR
AB - Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery.
AU - Müller, Jan
AU - Sixt, Michael K
ID - 1161
IS - 1
JF - Current Biology
SN - 09609822
TI - Cell migration: Making the waves
VL - 27
ER -
TY - JOUR
AB - Selected universal experimental properties of high-temperature superconducting (HTS) cuprates have been singled out in the last decade. One of the pivotal challenges in this field is the designation of a consistent interpretation framework within which we can describe quantitatively the universal features of those systems. Here we analyze in a detailed manner the principal experimental data and compare them quantitatively with the approach based on a single-band model of strongly correlated electrons supplemented with strong antiferromagnetic (super)exchange interaction (the so-called t−J−U model). The model rationale is provided by estimating its microscopic parameters on the basis of the three-band approach for the Cu-O plane. We use our original full Gutzwiller wave-function solution by going beyond the renormalized mean-field theory (RMFT) in a systematic manner. Our approach reproduces very well the observed hole doping (δ) dependence of the kinetic-energy gain in the superconducting phase, one of the principal non-Bardeen-Cooper-Schrieffer features of the cuprates. The calculated Fermi velocity in the nodal direction is practically δ-independent and its universal value agrees very well with that determined experimentally. Also, a weak doping dependence of the Fermi wave vector leads to an almost constant value of the effective mass in a pure superconducting phase which is both observed in experiment and reproduced within our approach. An assessment of the currently used models (t−J, Hubbard) is carried out and the results of the canonical RMFT as a zeroth-order solution are provided for comparison to illustrate the necessity of the introduced higher-order contributions.
AU - Spałek, Jozef
AU - Zegrodnik, Michał
AU - Kaczmarczyk, Jan
ID - 1162
IS - 2
JF - Physical Review B - Condensed Matter and Materials Physics
SN - 24699950
TI - Universal properties of high temperature superconductors from real space pairing t-J-U model and its quantitative comparison with experiment
VL - 95
ER -
TY - JOUR
AB - We investigate the effect of the electron-hole (e-h) symmetry breaking on d-wave superconductivity induced by non-local effects of correlations in the generalized Hubbard model. The symmetry breaking is introduced in a two-fold manner: by the next-to-nearest neighbor hopping of electrons and by the charge-bond interaction - the off-diagonal term of the Coulomb potential. Both terms lead to a pronounced asymmetry of the superconducting order parameter. The next-to-nearest neighbor hopping enhances superconductivity for h-doping, while diminishes it for e-doping. The charge-bond interaction alone leads to the opposite effect and, additionally, to the kinetic-energy gain upon condensation in the underdoped regime. With both terms included, with similar amplitudes, the height of the superconducting dome and the critical doping remain in favor of h-doping. The influence of the charge-bond interaction on deviations from symmetry of the shape of the gap at the Fermi surface in the momentum space is briefly discussed.
AU - Wysokiński, Marcin
AU - Kaczmarczyk, Jan
ID - 1163
IS - 8
JF - Journal of Physics: Condensed Matter
SN - 09538984
TI - Unconventional superconductivity in generalized Hubbard model role of electron–hole symmetry breaking terms
VL - 29
ER -
TY - JOUR
AB - Optimum experimental design theory has recently been extended for parameter estimation in copula models. The use of these models allows one to gain in flexibility by considering the model parameter set split into marginal and dependence parameters. However, this separation also leads to the natural issue of estimating only a subset of all model parameters. In this work, we treat this problem with the application of the (Formula presented.)-optimality to copula models. First, we provide an extension of the corresponding equivalence theory. Then, we analyze a wide range of flexible copula models to highlight the usefulness of (Formula presented.)-optimality in many possible scenarios. Finally, we discuss how the usage of the introduced design criterion also relates to the more general issue of copula selection and optimal design for model discrimination.
AU - Perrone, Elisa
AU - Rappold, Andreas
AU - Müller, Werner
ID - 1168
IS - 3
JF - Statistical Methods and Applications
TI - D inf s optimality in copula models
VL - 26
ER -
TY - JOUR
AB - Dispersal is a crucial factor in natural evolution, since it determines the habitat experienced by any population and defines the spatial scale of interactions between individuals. There is compelling evidence for systematic differences in dispersal characteristics within the same population, i.e., genotype-dependent dispersal. The consequences of genotype-dependent dispersal on other evolutionary phenomena, however, are poorly understood. In this article we investigate the effect of genotype-dependent dispersal on spatial gene frequency patterns, using a generalization of the classical diffusion model of selection and dispersal. Dispersal is characterized by the variance of dispersal (diffusion coefficient) and the mean displacement (directional advection term). We demonstrate that genotype-dependent dispersal may change the qualitative behavior of Fisher waves, which change from being “pulled” to being “pushed” wave fronts as the discrepancy in dispersal between genotypes increases. The speed of any wave is partitioned into components due to selection, genotype-dependent variance of dispersal, and genotype-dependent mean displacement. We apply our findings to wave fronts maintained by selection against heterozygotes. Furthermore, we identify a benefit of increased variance of dispersal, quantify its effect on the speed of the wave, and discuss the implications for the evolution of dispersal strategies.
AU - Novak, Sebastian
AU - Kollár, Richard
ID - 1169
IS - 1
JF - Genetics
SN - 00166731
TI - Spatial gene frequency waves under genotype dependent dispersal
VL - 205
ER -
TY - JOUR
AB - We introduce the Voronoi functional of a triangulation of a finite set of points in the Euclidean plane and prove that among all geometric triangulations of the point set, the Delaunay triangulation maximizes the functional. This result neither extends to topological triangulations in the plane nor to geometric triangulations in three and higher dimensions.
AU - Edelsbrunner, Herbert
AU - Glazyrin, Alexey
AU - Musin, Oleg
AU - Nikitenko, Anton
ID - 1173
IS - 5
JF - Combinatorica
SN - 02099683
TI - The Voronoi functional is maximized by the Delaunay triangulation in the plane
VL - 37
ER -
TY - CONF
AB - Security of cryptographic applications is typically defined by security games. The adversary, within certain resources, cannot win with probability much better than 0 (for unpredictability applications, like one-way functions) or much better than 1/2 (indistinguishability applications for instance encryption schemes). In so called squared-friendly applications the winning probability of the adversary, for different values of the application secret randomness, is not only close to 0 or 1/2 on average, but also concentrated in the sense that its second central moment is small. The class of squared-friendly applications, which contains all unpredictability applications and many indistinguishability applications, is particularly important for key derivation. Barak et al. observed that for square-friendly applications one can beat the "RT-bound", extracting secure keys with significantly smaller entropy loss. In turn Dodis and Yu showed that in squared-friendly applications one can directly use a "weak" key, which has only high entropy, as a secure key. In this paper we give sharp lower bounds on square security assuming security for "weak" keys. We show that any application which is either (a) secure with weak keys or (b) allows for entropy savings for keys derived by universal hashing, must be square-friendly. Quantitatively, our lower bounds match the positive results of Dodis and Yu and Barak et al. (TCC\'13, CRYPTO\'11) Hence, they can be understood as a general characterization of squared-friendly applications. While the positive results on squared-friendly applications where derived by one clever application of the Cauchy-Schwarz Inequality, for tight lower bounds we need more machinery. In our approach we use convex optimization techniques and some theory of circular matrices.
AU - Skórski, Maciej
ID - 1174
SN - 18688969
TI - Lower bounds on key derivation for square-friendly applications
VL - 66
ER -
TY - CONF
AB - We study space complexity and time-space trade-offs with a focus not on peak memory usage but on overall memory consumption throughout the computation. Such a cumulative space measure was introduced for the computational model of parallel black pebbling by [Alwen and Serbinenko ’15] as a tool for obtaining results in cryptography. We consider instead the non- deterministic black-white pebble game and prove optimal cumulative space lower bounds and trade-offs, where in order to minimize pebbling time the space has to remain large during a significant fraction of the pebbling. We also initiate the study of cumulative space in proof complexity, an area where other space complexity measures have been extensively studied during the last 10–15 years. Using and extending the connection between proof complexity and pebble games in [Ben-Sasson and Nordström ’08, ’11] we obtain several strong cumulative space results for (even parallel versions of) the resolution proof system, and outline some possible future directions of study of this, in our opinion, natural and interesting space measure.
AU - Alwen, Joel F
AU - De Rezende, Susanna
AU - Nordstrom, Jakob
AU - Vinyals, Marc
ED - Papadimitriou, Christos
ID - 1175
SN - 18688969
TI - Cumulative space in black-white pebbling and resolution
VL - 67
ER -
TY - CONF
AB - The algorithm Argon2i-B of Biryukov, Dinu and Khovratovich is currently being considered by the IRTF (Internet Research Task Force) as a new de-facto standard for password hashing. An older version (Argon2i-A) of the same algorithm was chosen as the winner of the recent Password Hashing Competition. An important competitor to Argon2i-B is the recently introduced Balloon Hashing (BH) algorithm of Corrigan-Gibs, Boneh and Schechter. A key security desiderata for any such algorithm is that evaluating it (even using a custom device) requires a large amount of memory amortized across multiple instances. Alwen and Blocki (CRYPTO 2016) introduced a class of theoretical attacks against Argon2i-A and BH. While these attacks yield large asymptotic reductions in the amount of memory, it was not, a priori, clear if (1) they can be extended to the newer Argon2i-B, (2) the attacks are effective on any algorithm for practical parameter ranges (e.g., 1GB of memory) and (3) if they can be effectively instantiated against any algorithm under realistic hardware constrains. In this work we answer all three of these questions in the affirmative for all three algorithms. This is also the first work to analyze the security of Argon2i-B. In more detail, we extend the theoretical attacks of Alwen and Blocki (CRYPTO 2016) to the recent Argon2i-B proposal demonstrating severe asymptotic deficiencies in its security. Next we introduce several novel heuristics for improving the attack's concrete memory efficiency even when on-chip memory bandwidth is bounded. We then simulate our attacks on randomly sampled Argon2i-A, Argon2i-B and BH instances and measure the resulting memory consumption for various practical parameter ranges and for a variety of upperbounds on the amount of parallelism available to the attacker. Finally we describe, implement, and test a new heuristic for applying the Alwen-Blocki attack to functions employing a technique developed by Corrigan-Gibs et al. for improving concrete security of memory-hard functions. We analyze the collected data and show the effects various parameters have on the memory consumption of the attack. In particular, we can draw several interesting conclusions about the level of security provided by these functions. · For the Alwen-Blocki attack to fail against practical memory parameters, Argon2i-B must be instantiated with more than 10 passes on memory - beyond the "paranoid" parameter setting in the current IRTF proposal. · The technique of Corrigan-Gibs for improving security can also be overcome by the Alwen-Blocki attack under realistic hardware constraints. · On a positive note, both the asymptotic and concrete security of Argon2i-B seem to improve on that of Argon2i-A.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
ID - 1176
SN - 978-150905761-0
TI - Towards practical attacks on Argon2i and balloon hashing
ER -