@article{5906, abstract = {We introduce a simple, exactly solvable strong-randomness renormalization group (RG) model for the many-body localization (MBL) transition in one dimension. Our approach relies on a family of RG flows parametrized by the asymmetry between thermal and localized phases. We identify the physical MBL transition in the limit of maximal asymmetry, reflecting the instability of MBL against rare thermal inclusions. We find a critical point that is localized with power-law distributed thermal inclusions. The typical size of critical inclusions remains finite at the transition, while the average size is logarithmically diverging. We propose a two-parameter scaling theory for the many-body localization transition that falls into the Kosterlitz-Thouless universality class, with the MBL phase corresponding to a stable line of fixed points with multifractal behavior.}, author = {Goremykina, Anna and Vasseur, Romain and Serbyn, Maksym}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {4}, publisher = {American Physical Society}, title = {{Analytically solvable renormalization group for the many-body localization transition}}, doi = {10.1103/physrevlett.122.040601}, volume = {122}, year = {2019}, } @article{6632, abstract = {We consider a two-component Bose gas in two dimensions at a low temperature with short-range repulsive interaction. In the coexistence phase where both components are superfluid, interspecies interactions induce a nondissipative drag between the two superfluid flows (Andreev-Bashkin effect). We show that this behavior leads to a modification of the usual Berezinskii-Kosterlitz-Thouless (BKT) transition in two dimensions. We extend the renormalization of the superfluid densities at finite temperature using the renormalization-group approach and find that the vortices of one component have a large influence on the superfluid properties of the other, mediated by the nondissipative drag. The extended BKT flow equations indicate that the occurrence of the vortex unbinding transition in one of the components can induce the breakdown of superfluidity also in the other, leading to a locking phenomenon for the critical temperatures of the two gases.}, author = {Karle, Volker and Defenu, Nicolò and Enss, Tilman}, issn = {24699934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Coupled superfluidity of binary Bose mixtures in two dimensions}}, doi = {10.1103/PhysRevA.99.063627}, volume = {99}, year = {2019}, } @article{7396, abstract = {The angular momentum of molecules, or, equivalently, their rotation in three-dimensional space, is ideally suited for quantum control. Molecular angular momentum is naturally quantized, time evolution is governed by a well-known Hamiltonian with only a few accurately known parameters, and transitions between rotational levels can be driven by external fields from various parts of the electromagnetic spectrum. Control over the rotational motion can be exerted in one-, two-, and many-body scenarios, thereby allowing one to probe Anderson localization, target stereoselectivity of bimolecular reactions, or encode quantum information to name just a few examples. The corresponding approaches to quantum control are pursued within separate, and typically disjoint, subfields of physics, including ultrafast science, cold collisions, ultracold gases, quantum information science, and condensed-matter physics. It is the purpose of this review to present the various control phenomena, which all rely on the same underlying physics, within a unified framework. To this end, recall the Hamiltonian for free rotations, assuming the rigid rotor approximation to be valid, and summarize the different ways for a rotor to interact with external electromagnetic fields. These interactions can be exploited for control—from achieving alignment, orientation, or laser cooling in a one-body framework, steering bimolecular collisions, or realizing a quantum computer or quantum simulator in the many-body setting.}, author = {Koch, Christiane P. and Lemeshko, Mikhail and Sugny, Dominique}, issn = {1539-0756}, journal = {Reviews of Modern Physics}, number = {3}, publisher = {American Physical Society}, title = {{Quantum control of molecular rotation}}, doi = {10.1103/revmodphys.91.035005}, volume = {91}, year = {2019}, } @inproceedings{7606, abstract = {We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound.}, author = {Hledik, Michal and Sokolowski, Thomas R and Tkačik, Gašper}, booktitle = {IEEE Information Theory Workshop, ITW 2019}, isbn = {9781538669006}, location = {Visby, Sweden}, publisher = {IEEE}, title = {{A tight upper bound on mutual information}}, doi = {10.1109/ITW44776.2019.8989292}, year = {2019}, } @inproceedings{6933, abstract = {We design fast deterministic algorithms for distance computation in the CONGESTED CLIQUE model. Our key contributions include: - A (2+ε)-approximation for all-pairs shortest paths problem in O(log²n / ε) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model. - A (1+ε)-approximation for multi-source shortest paths problem from O(√n) sources in O(log² n / ε) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size. Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in Õ(n^{1/6}) rounds.}, author = {Censor-Hillel, Keren and Dory, Michal and Korhonen, Janne and Leitersdorf, Dean}, booktitle = {Proceedings of the 2019 ACM Symposium on Principles of Distributed Computin}, isbn = {9781450362177}, location = {Toronto, ON, Canada}, pages = {74--83}, publisher = {ACM}, title = {{Fast approximate shortest paths in the congested clique}}, doi = {10.1145/3293611.3331633}, year = {2019}, } @unpublished{15147, abstract = {Circadian rhythms are generated by a transcription-based feedback loop where CLOCK:BMAL1 drive transcription of their repressors (PER1/2, CRY1/2), which bind to CLOCK:BMAL1 to close the feedback loop with ~24-hour periodicity. Here we identify a key biochemical and structural difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. While both cryptochromes bind the BMAL1 transactivation domain with similar affinity to sequester it from coactivators, CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We identify a dynamic loop in the secondary pocket that regulates differential binding of cryptochromes to the PAS domain core. Notably, PER2 binding remodels this loop in CRY2 to enhance its affinity for CLOCK:BMAL1, explaining why CRY2 forms an obligate heterodimer with PER2, while CRY1 is capable of repressing CLOCK:BMAL1 both with and without PER2.}, author = {Fribourgh, Jennifer L. and Srivastava, Ashutosh and Sandate, Colby R. and Michael, Alicia and Hsu, Peter L. and Rakers, Christin and Nguyen, Leslee T. and Torgrimson, Megan R. and Parico, Gian Carlo G. and Tripathi, Sarvind and Zheng, Ning and Lander, Gabriel C. and Hirota, Tsuyoshi and Tama, Florence and Partch, Carrie L.}, booktitle = {bioRxiv}, title = {{Protein dynamics regulate distinct biochemical properties of cryptochromes in mammalian circadian rhythms}}, doi = {10.1101/740464}, year = {2019}, } @phdthesis{6392, abstract = {The regulation of gene expression is one of the most fundamental processes in living systems. In recent years, thanks to advances in sequencing technology and automation, it has become possible to study gene expression quantitatively, genome-wide and in high-throughput. This leads to the possibility of exploring changes in gene expression in the context of many external perturbations and their combinations, and thus of characterising the basic principles governing gene regulation. In this thesis, I present quantitative experimental approaches to studying transcriptional and protein level changes in response to combinatorial drug treatment, as well as a theoretical data-driven approach to analysing thermodynamic principles guiding transcription of protein coding genes. In the first part of this work, I present a novel methodological framework for quantifying gene expression changes in drug combinations, termed isogrowth profiling. External perturbations through small molecule drugs influence the growth rate of the cell, leading to wide-ranging changes in cellular physiology and gene expression. This confounds the gene expression changes specifically elicited by the particular drug. Combinatorial perturbations, owing to the increased stress they exert, influence the growth rate even more strongly and hence suffer the convolution problem to a greater extent when measuring gene expression changes. Isogrowth profiling is a way to experimentally abstract non-specific, growth rate related changes, by performing the measurement using varying ratios of two drugs at such concentrations that the overall inhibition rate is constant. Using a robotic setup for automated high-throughput re-dilution culture of Saccharomyces cerevisiae, the budding yeast, I investigate all pairwise interactions of four small molecule drugs through sequencing RNA along a growth isobole. Through principal component analysis, I demonstrate here that isogrowth profiling can uncover drug-specific as well as drug-interaction-specific gene expression changes. I show that drug-interaction-specific gene expression changes can be used for prediction of higher-order drug interactions. I propose a simplified generalised framework of isogrowth profiling, with few measurements needed for each drug pair, enabling the broad application of isogrowth profiling to high-throughput screening of inhibitors of cellular growth and beyond. Such high-throughput screenings of gene expression changes specific to pairwise drug interactions will be instrumental for predicting the higher-order interactions of the drugs. In the second part of this work, I extend isogrowth profiling to single-cell measurements of gene expression, characterising population heterogeneity in the budding yeast in response to combinatorial drug perturbation while controlling for non-specific growth rate effects. Through flow cytometry of strains with protein products fused to green fluorescent protein, I discover multiple proteins with bi-modally distributed expression levels in the population in response to drug treatment. I characterize more closely the effect of an ionic stressor, lithium chloride, and find that it inhibits the splicing of mRNA, most strongly affecting ribosomal protein transcripts and leading to a bi-stable behaviour of a small ribosomal subunit protein Rps22B. Time-lapse microscopy of a microfluidic culture system revealed that the induced Rps22B heterogeneity leads to preferential survival of Rps22B-low cells after long starvation, but to preferential proliferation of Rps22B-high cells after short starvation. Overall, this suggests that yeast cells might use splicing of ribosomal genes for bet-hedging in fluctuating environments. I give specific examples of how further exploration of cellular heterogeneity in yeast in response to external perturbation has the potential to reveal yet-undiscovered gene regulation circuitry. In the last part of this thesis, a re-analysis of a published sequencing dataset of nascent elongating transcripts is used to characterise the thermodynamic constraints for RNA polymerase II (RNAP) elongation. Population-level data on RNAP position throughout the transcribed genome with single nucleotide resolution are used to infer the sequence specific thermodynamic determinants of RNAP pausing and backtracking. This analysis reveals that the basepairing strength of the eight nucleotide-long RNA:DNA duplex relative to the basepairing strength of the same sequence when in DNA:DNA duplex, and the change in this quantity during RNA polymerase movement, is the key determinant of RNAP pausing. This is true for RNAP pausing while elongating, but also of RNAP pausing while backtracking and of the backtracking length. The quantitative dependence of RNAP pausing on basepairing energetics is used to infer the increase in pausing due to transcriptional mismatches, leading to a hypothesis that pervasive RNA polymerase II pausing is due to basepairing energetics, as an evolutionary cost for increased RNA polymerase II fidelity. This work advances our understanding of the general principles governing gene expression, with the goal of making computational predictions of single-cell gene expression responses to combinatorial perturbations based on the individual perturbations possible. This ability would substantially facilitate the design of drug combination treatments and, in the long term, lead to our increased ability to more generally design targeted manipulations to any biological system. }, author = {Lukacisin, Martin}, isbn = {978-3-99078-001-5}, issn = {2663-337X}, pages = {103}, publisher = {IST Austria}, title = {{Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory}}, doi = {10.15479/AT:ISTA:6392}, year = {2019}, } @phdthesis{6435, abstract = {Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ cells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are in charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units (i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''. Social immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social immunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop the collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of social immune responses have been dissected, but many more questions remain open. I present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals carrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate. The second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive and challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation. In addition to the two experimental chapters, this thesis includes a co-authored published review on organisational immunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built, identify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in two collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant behaviour.}, author = {Casillas Perez, Barbara E}, issn = {2663-337X}, keywords = {Social Immunity, Sanitary care, Social Insects, Organisational Immunity, Colony development, Multi-target tracking}, pages = {183}, publisher = {Institute of Science and Technology Austria}, title = {{Collective defenses of garden ants against a fungal pathogen}}, doi = {10.15479/AT:ISTA:6435}, year = {2019}, } @phdthesis{6269, abstract = {Clathrin-Mediated Endocytosis (CME) is an aspect of cellular trafficking that is constantly regulated for mediating developmental and physiological responses. The main aim of my thesis is to decipher the basic mechanisms of CME and post-endocytic trafficking in the whole multicellular organ systems of Arabidopsis. The first chapter of my thesis describes the search for new components involved in CME. Tandem affinity purification was conducted using CLC and its interacting partners were identified. Amongst the identified proteins were the Auxilin-likes1 and 2 (Axl1/2), putative uncoating factors, for which we made a full functional analysis. Over-expression of Axl1/2 causes extreme modifications in the dynamics of the machinery proteins and inhibition of endocytosis altogether. However the loss of function of the axl1/2 did not present any cellular or physiological phenotype, meaning Auxilin-likes do not form the major uncoating machinery. The second chapter of my thesis describes the establishment/utilisation of techniques to capture the dynamicity and the complexity of CME and post-endocytic trafficking. We have studied the development of endocytic pits at the PM – specifically, the mode of membrane remodeling during pit development and the role of actin in it, given plant cells possess high turgor pressure. Utilizing the improved z-resolution of TIRF and VAEM techniques, we captured the time-lapse of the endocytic events at the plasma membrane; and using particle detection software, we quantitatively analysed all the endocytic trajectories in an unbiased way to obtain the endocytic rate of the system. This together with the direct analysis of cargo internalisation from the PM provided an estimate on the endocytic potential of the cell. We also developed a methodology for ultrastructural analysis of different populations of Clathrin-Coated Structures (CCSs) in both PM and endomembranes in unroofed protoplasts. Structural analysis, together with the intensity profile of CCSs at the PM show that the mode of CCP development at the PM follows ‘Constant curvature model’; meaning that clathrin polymerisation energy is a major contributing factor of membrane remodeling. In addition, other analyses clearly show that actin is not required for membrane remodeling during invagination or any other step of CCP development, despite the prevalent high turgor pressure. However, actin is essential in orchestrating the post-endocytic trafficking of CCVs facilitating the EE formation. We also observed that the uncoating process post-endocytosis is not immediate; an alternative mechanism of uncoating – Sequential multi-step process – functions in the cell. Finally we also looked at one of the important physiological stimuli modulating the process – hormone, auxin. auxin has been known to influence CME before. We have made a detailed study on the concentration-time based effect of auxin on the machinery proteins, CCP development, and the specificity of cargoes endocytosed. To this end, we saw no general effect of auxin on CME at earlier time points. However, very low concentration of IAA, such as 50nM, accelerates endocytosis of specifically PIN2 through CME. Such a tight regulatory control with high specificity to PIN2 could be essential in modulating its polarity. }, author = {Narasimhan, Madhumitha}, issn = {2663-337X}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants }}, doi = {10.15479/at:ista:th1075}, year = {2019}, } @inproceedings{11222, author = {Kim, Olena and Borges Merjane, Carolina and Jonas, Peter M}, booktitle = {Intrinsic Activity}, issn = {2309-8503}, keywords = {hippocampus, mossy fibers, readily releasable pool, electron microscopy}, location = {Innsbruck, Austria}, number = {Suppl. 1}, publisher = {Austrian Pharmacological Society}, title = {{Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy}}, doi = {10.25006/ia.7.s1-a3.27}, volume = {7}, year = {2019}, } @phdthesis{6947, abstract = {Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues.}, author = {Assen, Frank P}, issn = {2663-337X}, pages = {142}, publisher = {Institute of Science and Technology Austria}, title = {{Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking}}, doi = {10.15479/AT:ISTA:6947}, year = {2019}, } @phdthesis{6849, abstract = {Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. }, author = {Rangel Guerrero, Dámaris K}, isbn = {9783990780039}, issn = {2663-337X}, pages = {97}, publisher = {Institute of Science and Technology Austria}, title = {{The role of CCK-interneurons in regulating hippocampal network dynamics}}, doi = {10.15479/AT:ISTA:6849}, year = {2019}, } @article{6351, abstract = {A process of restorative patterning in plant roots correctly replaces eliminated cells to heal local injuries despite the absence of cell migration, which underpins wound healing in animals. Patterning in plants relies on oriented cell divisions and acquisition of specific cell identities. Plants regularly endure wounds caused by abiotic or biotic environmental stimuli and have developed extraordinary abilities to restore their tissues after injuries. Here, we provide insight into a mechanism of restorative patterning that repairs tissues after wounding. Laser-assisted elimination of different cells in Arabidopsis root combined with live-imaging tracking during vertical growth allowed analysis of the regeneration processes in vivo. Specifically, the cells adjacent to the inner side of the injury re-activated their stem cell transcriptional programs. They accelerated their progression through cell cycle, coordinately changed the cell division orientation, and ultimately acquired de novo the correct cell fates to replace missing cells. These observations highlight existence of unknown intercellular positional signaling and demonstrate the capability of specified cells to re-acquire stem cell programs as a crucial part of the plant-specific mechanism of wound healing.}, author = {Marhavá, Petra and Hörmayer, Lukas and Yoshida, Saiko and Marhavy, Peter and Benková, Eva and Friml, Jiří}, issn = {10974172}, journal = {Cell}, number = {4}, pages = {957--969.e13}, publisher = {Elsevier}, title = {{Re-activation of stem cell pathways for pattern restoration in plant wound healing}}, doi = {10.1016/j.cell.2019.04.015}, volume = {177}, year = {2019}, } @article{6943, abstract = {Plants as sessile organisms are constantly under attack by herbivores, rough environmental situations, or mechanical pressure. These challenges often lead to the induction of wounds or destruction of already specified and developed tissues. Additionally, wounding makes plants vulnerable to invasion by pathogens, which is why wound signalling often triggers specific defence responses. To stay competitive or, eventually, survive under these circumstances, plants need to regenerate efficiently, which in rigid, tissue migration-incompatible plant tissues requires post-embryonic patterning and organogenesis. Now, several studies used laser-assisted single cell ablation in the Arabidopsis root tip as a minimal wounding proxy. Here, we discuss their findings and put them into context of a broader spectrum of wound signalling, pathogen responses and tissue as well as organ regeneration.}, author = {Hörmayer, Lukas and Friml, Jiří}, issn = {1369-5266}, journal = {Current Opinion in Plant Biology}, pages = {124--130}, publisher = {Elsevier}, title = {{Targeted cell ablation-based insights into wound healing and restorative patterning}}, doi = {10.1016/j.pbi.2019.08.006}, volume = {52}, year = {2019}, } @article{7391, abstract = {Electron microscopy (EM) is a technology that enables visualization of single proteins at a nanometer resolution. However, current protein analysis by EM mainly relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised by large size of antibody, precluding precise detection of protein location in biological samples. Here, we develop a specific chemical labeling method for EM detection of proteins at single-molecular level. Rational design of α-helical peptide tag and probe structure provided a complementary reaction pair that enabled specific cysteine conjugation of the tag. The developed chemical labeling with gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency and detectability of high-density clusters of tag-fused G protein-coupled receptors in freeze-fracture replicas compared with immunogold labeling. Furthermore, in ultrathin sections, the spatial resolution of the chemical labeling was significantly higher than that of antibody-mediated labeling. These results demonstrate substantial advantages of the chemical labeling approach for single protein visualization by EM.}, author = {Tabata, Shigekazu and Jevtic, Marijo and Kurashige, Nobutaka and Fuchida, Hirokazu and Kido, Munetsugu and Tani, Kazushi and Zenmyo, Naoki and Uchinomiya, Shohei and Harada, Harumi and Itakura, Makoto and Hamachi, Itaru and Shigemoto, Ryuichi and Ojida, Akio}, issn = {2589-0042}, journal = {iScience}, number = {12}, pages = {256--268}, publisher = {Elsevier}, title = {{Electron microscopic detection of single membrane proteins by a specific chemical labeling}}, doi = {10.1016/j.isci.2019.11.025}, volume = {22}, year = {2019}, } @article{6848, abstract = {Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9.}, author = {Kampjut, Domen and Sazanov, Leonid A}, issn = {1476-4687}, journal = {Nature}, number = {7773}, pages = {291–295}, publisher = {Springer Nature}, title = {{Structure and mechanism of mitochondrial proton-translocating transhydrogenase}}, doi = {10.1038/s41586-019-1519-2}, volume = {573}, year = {2019}, } @article{6194, abstract = {Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space.}, author = {Boccara, Charlotte N. and Nardin, Michele and Stella, Federico and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {1095-9203}, journal = {Science}, number = {6434}, pages = {1443--1447}, publisher = {American Association for the Advancement of Science}, title = {{The entorhinal cognitive map is attracted to goals}}, doi = {10.1126/science.aav4837}, volume = {363}, year = {2019}, } @phdthesis{7132, abstract = {A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta. Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing.}, author = {Mckenzie, Catherine}, issn = {2663-337X}, pages = {95}, publisher = {Institute of Science and Technology Austria}, title = {{Design and characterization of methods and biological components to realize synthetic neurotransmission}}, doi = {10.15479/at:ista:7132}, year = {2019}, } @article{5949, abstract = {Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.}, author = {Käfer, Karola and Malagon-Vina, Hugo and Dickerson, Desiree and O'Neill, Joseph and Trossbach, Svenja V. and Korth, Carsten and Csicsvari, Jozsef L}, journal = {Hippocampus}, number = {9}, pages = {802--816}, publisher = {Wiley}, title = {{Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization}}, doi = {10.1002/hipo.23076}, volume = {29}, year = {2019}, } @phdthesis{6825, abstract = {The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions. With tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay. We found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by maze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between cell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC trajectory-replay at the goal positively correlated with rule-switching performance. Finally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. }, author = {Käfer, Karola}, issn = {2663-337X}, pages = {89}, publisher = {Institute of Science and Technology Austria}, title = {{The hippocampus and medial prefrontal cortex during flexible behavior}}, doi = {10.15479/AT:ISTA:6825}, year = {2019}, } @article{6713, abstract = {Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.}, author = {Castro, João Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and Kučka, Marek and Beluch, William H. and Naumann, Ronald and Skuplik, Isabella and Cobb, John and Barton, Nicholas H and Rolian, Campbell and Chan, Yingguang Frank}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice}}, doi = {10.7554/eLife.42014}, volume = {8}, year = {2019}, } @unpublished{10065, abstract = {We study double quantum dots in a Ge/SiGe heterostructure and test their maturity towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability, from two single quantum dots to a double quantum dot. We measure Pauli spin blockade and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for sensing charge transitions in the double quantum dot at interest. In conclusion, Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit.}, author = {Hofmann, Andrea C and Jirovec, Daniel and Borovkov, Maxim and Prieto Gonzalez, Ivan and Ballabio, Andrea and Frigerio, Jacopo and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, booktitle = {arXiv}, title = {{Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits}}, doi = {10.48550/arXiv.1910.05841}, year = {2019}, } @article{6187, abstract = {Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.}, author = {Valosková, Katarina and Biebl, Julia and Roblek, Marko and Emtenani, Shamsi and György, Attila and Misova, Michaela and Ratheesh, Aparna and Rodrigues, Patricia and Shkarina, Katerina and Larsen, Ida Signe Bohse and Vakhrushev, Sergey Y and Clausen, Henrik and Siekhaus, Daria E}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion}}, doi = {10.7554/elife.41801}, volume = {8}, year = {2019}, } @phdthesis{6546, abstract = {Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis. }, author = {Valosková, Katarina}, issn = {2663-337X}, pages = {141}, publisher = {Institute of Science and Technology Austria}, title = {{The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration}}, doi = {10.15479/AT:ISTA:6546}, year = {2019}, } @phdthesis{6363, abstract = {Distinguishing between similar experiences is achieved by the brain in a process called pattern separation. In the hippocampus, pattern separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into non-overlapping output firing patterns. Winners-take-all (WTA) mechanism is a theoretical model for pattern separation in which a "winner" cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined but less abundant than PV+interneurons–GC connectivity, leading to an asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. This process relied on lateral inhibition, fast-signaling properties of PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. }, author = {Espinoza Martinez, Claudia }, isbn = {978-3-99078-000-8}, issn = {2663-337X}, pages = {140}, publisher = {Institute of Science and Technology Austria}, title = {{Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits}}, doi = {10.15479/AT:ISTA:6363}, year = {2019}, } @inproceedings{6780, abstract = {In this work, we consider the almost-sure termination problem for probabilistic programs that asks whether a given probabilistic program terminates with probability 1. Scalable approaches for program analysis often rely on modularity as their theoretical basis. In non-probabilistic programs, the classical variant rule (V-rule) of Floyd-Hoare logic provides the foundation for modular analysis. Extension of this rule to almost-sure termination of probabilistic programs is quite tricky, and a probabilistic variant was proposed in [16]. While the proposed probabilistic variant cautiously addresses the key issue of integrability, we show that the proposed modular rule is still not sound for almost-sure termination of probabilistic programs. Besides establishing unsoundness of the previous rule, our contributions are as follows: First, we present a sound modular rule for almost-sure termination of probabilistic programs. Our approach is based on a novel notion of descent supermartingales. Second, for algorithmic approaches, we consider descent supermartingales that are linear and show that they can be synthesized in polynomial time. Finally, we present experimental results on a variety of benchmarks and several natural examples that model various types of nested while loops in probabilistic programs and demonstrate that our approach is able to efficiently prove their almost-sure termination property}, author = {Huang, Mingzhang and Fu, Hongfei and Chatterjee, Krishnendu and Goharshady, Amir Kafshdar}, booktitle = {Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications }, location = {Athens, Greece}, publisher = {ACM}, title = {{Modular verification for almost-sure termination of probabilistic programs}}, doi = {10.1145/3360555}, volume = {3}, year = {2019}, } @article{6380, abstract = {There is a huge gap between the speeds of modern caches and main memories, and therefore cache misses account for a considerable loss of efficiency in programs. The predominant technique to address this issue has been Data Packing: data elements that are frequently accessed within time proximity are packed into the same cache block, thereby minimizing accesses to the main memory. We consider the algorithmic problem of Data Packing on a two-level memory system. Given a reference sequence R of accesses to data elements, the task is to partition the elements into cache blocks such that the number of cache misses on R is minimized. The problem is notoriously difficult: it is NP-hard even when the cache has size 1, and is hard to approximate for any cache size larger than 4. Therefore, all existing techniques for Data Packing are based on heuristics and lack theoretical guarantees. In this work, we present the first positive theoretical results for Data Packing, along with new and stronger negative results. We consider the problem under the lens of the underlying access hypergraphs, which are hypergraphs of affinities between the data elements, where the order of an access hypergraph corresponds to the size of the affinity group. We study the problem parameterized by the treewidth of access hypergraphs, which is a standard notion in graph theory to measure the closeness of a graph to a tree. Our main results are as follows: We show there is a number q* depending on the cache parameters such that (a) if the access hypergraph of order q* has constant treewidth, then there is a linear-time algorithm for Data Packing; (b)the Data Packing problem remains NP-hard even if the access hypergraph of order q*-1 has constant treewidth. Thus, we establish a fine-grained dichotomy depending on a single parameter, namely, the highest order among access hypegraphs that have constant treewidth; and establish the optimal value q* of this parameter. Finally, we present an experimental evaluation of a prototype implementation of our algorithm. Our results demonstrate that, in practice, access hypergraphs of many commonly-used algorithms have small treewidth. We compare our approach with several state-of-the-art heuristic-based algorithms and show that our algorithm leads to significantly fewer cache-misses. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Okati, Nastaran and Pavlogiannis, Andreas}, issn = {2475-1421}, journal = {Proceedings of the ACM on Programming Languages}, number = {POPL}, publisher = {ACM}, title = {{Efficient parameterized algorithms for data packing}}, doi = {10.1145/3290366}, volume = {3}, year = {2019}, } @inproceedings{6056, abstract = {In today's programmable blockchains, smart contracts are limited to being deterministic and non-probabilistic. This lack of randomness is a consequential limitation, given that a wide variety of real-world financial contracts, such as casino games and lotteries, depend entirely on randomness. As a result, several ad-hoc random number generation approaches have been developed to be used in smart contracts. These include ideas such as using an oracle or relying on the block hash. However, these approaches are manipulatable, i.e. their output can be tampered with by parties who might not be neutral, such as the owner of the oracle or the miners.We propose a novel game-theoretic approach for generating provably unmanipulatable pseudorandom numbers on the blockchain. Our approach allows smart contracts to access a trustworthy source of randomness that does not rely on potentially compromised miners or oracles, hence enabling the creation of a new generation of smart contracts that are not limited to being non-probabilistic and can be drawn from the much more general class of probabilistic programs.}, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Pourdamghani, Arash}, booktitle = {IEEE International Conference on Blockchain and Cryptocurrency}, location = {Seoul, Korea}, publisher = {IEEE}, title = {{Probabilistic smart contracts: Secure randomness on the blockchain}}, doi = {10.1109/BLOC.2019.8751326}, year = {2019}, } @inproceedings{6378, abstract = {In today's cryptocurrencies, Hashcash proof of work is the most commonly-adopted approach to mining. In Hashcash, when a miner decides to add a block to the chain, she has to solve the difficult computational puzzle of inverting a hash function. While Hashcash has been successfully adopted in both Bitcoin and Ethereum, it has attracted significant and harsh criticism due to its massive waste of electricity, its carbon footprint and environmental effects, and the inherent lack of usefulness in inverting a hash function. Various other mining protocols have been suggested, including proof of stake, in which a miner's chance of adding the next block is proportional to her current balance. However, such protocols lead to a higher entry cost for new miners who might not still have any stake in the cryptocurrency, and can in the worst case lead to an oligopoly, where the rich have complete control over mining. In this paper, we propose Hybrid Mining: a new mining protocol that combines solving real-world useful problems with Hashcash. Our protocol allows new miners to join the network by taking part in Hashcash mining without having to own an initial stake. It also allows nodes of the network to submit hard computational problems whose solutions are of interest in the real world, e.g.~protein folding problems. Then, miners can choose to compete in solving these problems, in lieu of Hashcash, for adding a new block. Hence, Hybrid Mining incentivizes miners to solve useful problems, such as hard computational problems arising in biology, in a distributed manner. It also gives researchers in other areas an easy-to-use tool to outsource their hard computations to the blockchain network, which has enormous computational power, by paying a reward to the miner who solves the problem for them. Moreover, our protocol provides strong security guarantees and is at least as resilient to double spending as Bitcoin.}, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Pourdamghani, Arash}, booktitle = {Proceedings of the 34th ACM Symposium on Applied Computing}, isbn = {9781450359337}, location = {Limassol, Cyprus}, pages = {374--381}, publisher = {ACM}, title = {{Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving}}, doi = {10.1145/3297280.3297319}, volume = {Part F147772}, year = {2019}, } @inproceedings{6175, abstract = {We consider the problem of expected cost analysis over nondeterministic probabilistic programs, which aims at automated methods for analyzing the resource-usage of such programs. Previous approaches for this problem could only handle nonnegative bounded costs. However, in many scenarios, such as queuing networks or analysis of cryptocurrency protocols, both positive and negative costs are necessary and the costs are unbounded as well. In this work, we present a sound and efficient approach to obtain polynomial bounds on the expected accumulated cost of nondeterministic probabilistic programs. Our approach can handle (a) general positive and negative costs with bounded updates in variables; and (b) nonnegative costs with general updates to variables. We show that several natural examples which could not be handled by previous approaches are captured in our framework. Moreover, our approach leads to an efficient polynomial-time algorithm, while no previous approach for cost analysis of probabilistic programs could guarantee polynomial runtime. Finally, we show the effectiveness of our approach using experimental results on a variety of programs for which we efficiently synthesize tight resource-usage bounds.}, author = {Wang, Peixin and Fu, Hongfei and Goharshady, Amir Kafshdar and Chatterjee, Krishnendu and Qin, Xudong and Shi, Wenjun}, booktitle = {PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation}, keywords = {Program Cost Analysis, Program Termination, Probabilistic Programs, Martingales}, location = {Phoenix, AZ, United States}, pages = {204--220}, publisher = {Association for Computing Machinery}, title = {{Cost analysis of nondeterministic probabilistic programs}}, doi = {10.1145/3314221.3314581}, year = {2019}, } @inproceedings{6490, abstract = {Smart contracts are programs that are stored and executed on the Blockchain and can receive, manage and transfer money (cryptocurrency units). Two important problems regarding smart contracts are formal analysis and compiler optimization. Formal analysis is extremely important, because smart contracts hold funds worth billions of dollars and their code is immutable after deployment. Hence, an undetected bug can cause significant financial losses. Compiler optimization is also crucial, because every action of a smart contract has to be executed by every node in the Blockchain network. Therefore, optimizations in compiling smart contracts can lead to significant savings in computation, time and energy. Two classical approaches in program analysis and compiler optimization are intraprocedural and interprocedural analysis. In intraprocedural analysis, each function is analyzed separately, while interprocedural analysis considers the entire program. In both cases, the analyses are usually reduced to graph problems over the control flow graph (CFG) of the program. These graph problems are often computationally expensive. Hence, there has been ample research on exploiting structural properties of CFGs for efficient algorithms. One such well-studied property is the treewidth, which is a measure of tree-likeness of graphs. It is known that intraprocedural CFGs of structured programs have treewidth at most 6, whereas the interprocedural treewidth cannot be bounded. This result has been used as a basis for many efficient intraprocedural analyses. In this paper, we explore the idea of exploiting the treewidth of smart contracts for formal analysis and compiler optimization. First, similar to classical programs, we show that the intraprocedural treewidth of structured Solidity and Vyper smart contracts is at most 9. Second, for global analysis, we prove that the interprocedural treewidth of structured smart contracts is bounded by 10 and, in sharp contrast with classical programs, treewidth-based algorithms can be easily applied for interprocedural analysis. Finally, we supplement our theoretical results with experiments using a tool we implemented for computing treewidth of smart contracts and show that the treewidth is much lower in practice. We use 36,764 real-world Ethereum smart contracts as benchmarks and find that they have an average treewidth of at most 3.35 for the intraprocedural case and 3.65 for the interprocedural case. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goharshady, Ehsan Kafshdar}, booktitle = {Proceedings of the 34th ACM Symposium on Applied Computing}, isbn = {9781450359337}, location = {Limassol, Cyprus}, pages = {400--408}, publisher = {ACM}, title = {{The treewidth of smart contracts}}, doi = {10.1145/3297280.3297322}, volume = {Part F147772}, year = {2019}, } @article{7158, abstract = {Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth. Our main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches. }, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Goyal, Prateesh and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth}}, doi = {10.1145/3363525}, volume = {41}, year = {2019}, } @article{7014, abstract = {We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of nonrecursive programs. First, we apply ranking functions to recursion, resulting in measure functions. We show that measure functions provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in nonpolynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form $\mathcal{O}(n\log n)$ as well as $\mathcal{O}(n^r)$ where $r$ is not an integer. We present experimental results to demonstrate that our approach can obtain efficiently worst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the divide-and-conquer algorithm for the Closest-Pair problem, where we obtain $\mathcal{O}(n \log n)$ worst-case bound, and (ii) Karatsuba's algorithm for polynomial multiplication and Strassen's algorithm for matrix multiplication, where we obtain $\mathcal{O}(n^r)$ bound such that $r$ is not an integer and close to the best-known bounds for the respective algorithms.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar}, journal = {ACM Transactions on Programming Languages and Systems}, number = {4}, publisher = {ACM}, title = {{Non-polynomial worst-case analysis of recursive programs}}, doi = {10.1145/3339984}, volume = {41}, year = {2019}, } @article{6486, abstract = {Based on a novel control scheme, where a steady modification of the streamwise velocity profile leads to complete relaminarization of initially fully turbulent pipe flow, we investigate the applicability and usefulness of custom-shaped honeycombs for such control. The custom-shaped honeycombs are used as stationary flow management devices which generate specific modifications of the streamwise velocity profile. Stereoscopic particle image velocimetry and pressure drop measurements are used to investigate and capture the development of the relaminarizing flow downstream these devices. We compare the performance of straight (constant length across the radius of the pipe) honeycombs with custom-shaped ones (variable length across the radius) and try to determine the optimal shape for maximal relaminarization at minimal pressure loss. The optimally modified streamwise velocity profile is found to be M-shaped, and the maximum attainable Reynolds number for total relaminarization is found to be of the order of 10,000. Consequently, the respective reduction in skin friction downstream of the device is almost by a factor of 5. The break-even point, where the additional pressure drop caused by the device is balanced by the savings due to relaminarization and a net gain is obtained, corresponds to a downstream stretch of distances as low as approximately 100 pipe diameters of laminar flow.}, author = {Kühnen, Jakob and Scarselli, Davide and Hof, Björn}, issn = {1528901X}, journal = {Journal of Fluids Engineering}, number = {11}, publisher = {ASME}, title = {{Relaminarization of pipe flow by means of 3D-printed shaped honeycombs}}, doi = {10.1115/1.4043494}, volume = {141}, year = {2019}, } @article{6228, abstract = {Following the recent observation that turbulent pipe flow can be relaminarised bya relatively simple modification of the mean velocity profile, we here carry out aquantitative experimental investigation of this phenomenon. Our study confirms thata flat velocity profile leads to a collapse of turbulence and in order to achieve theblunted profile shape, we employ a moving pipe segment that is briefly and rapidlyshifted in the streamwise direction. The relaminarisation threshold and the minimumshift length and speeds are determined as a function of Reynolds number. Althoughturbulence is still active after the acceleration phase, the modulated profile possessesa severely decreased lift-up potential as measured by transient growth. As shown,this results in an exponential decay of fluctuations and the flow relaminarises. Whilethis method can be easily applied at low to moderate flow speeds, the minimumstreamwise length over which the acceleration needs to act increases linearly with theReynolds number.}, author = {Scarselli, Davide and Kühnen, Jakob and Hof, Björn}, issn = {14697645}, journal = {Journal of Fluid Mechanics}, pages = {934--948}, publisher = {Cambridge University Press}, title = {{Relaminarising pipe flow by wall movement}}, doi = {10.1017/jfm.2019.191}, volume = {867}, year = {2019}, } @article{6260, abstract = {Polar auxin transport plays a pivotal role in plant growth and development. PIN auxin efflux carriers regulate directional auxin movement by establishing local auxin maxima, minima, and gradients that drive multiple developmental processes and responses to environmental signals. Auxin has been proposed to modulate its own transport by regulating subcellular PIN trafficking via processes such as clathrin-mediated PIN endocytosis and constitutive recycling. Here, we further investigated the mechanisms by which auxin affects PIN trafficking by screening auxin analogs and identified pinstatic acid (PISA) as a positive modulator of polar auxin transport in Arabidopsis thaliana. PISA had an auxin-like effect on hypocotyl elongation and adventitious root formation via positive regulation of auxin transport. PISA did not activate SCFTIR1/AFB signaling and yet induced PIN accumulation at the cell surface by inhibiting PIN internalization from the plasma membrane. This work demonstrates PISA to be a promising chemical tool to dissect the regulatory mechanisms behind subcellular PIN trafficking and auxin transport.}, author = {Oochi, A and Hajny, Jakub and Fukui, K and Nakao, Y and Gallei, Michelle C and Quareshy, M and Takahashi, K and Kinoshita, T and Harborough, SR and Kepinski, S and Kasahara, H and Napier, RM and Friml, Jiří and Hayashi, KI}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {1152--1165}, publisher = {ASPB}, title = {{Pinstatic acid promotes auxin transport by inhibiting PIN internalization}}, doi = {10.1104/pp.19.00201}, volume = {180}, year = {2019}, } @article{6508, abstract = {Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation.}, author = {Shamipour, Shayan and Kardos, Roland and Xue, Shi-lei and Hof, Björn and Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, issn = {10974172}, journal = {Cell}, number = {6}, pages = {1463--1479.e18}, publisher = {Elsevier}, title = {{Bulk actin dynamics drive phase segregation in zebrafish oocytes}}, doi = {10.1016/j.cell.2019.04.030}, volume = {177}, year = {2019}, } @article{7001, author = {Schwayer, Cornelia and Shamipour, Shayan and Pranjic-Ferscha, Kornelija and Schauer, Alexandra and Balda, M and Tada, M and Matter, K and Heisenberg, Carl-Philipp J}, issn = {1097-4172}, journal = {Cell}, number = {4}, pages = {937--952.e18}, publisher = {Cell Press}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.1016/j.cell.2019.10.006}, volume = {179}, year = {2019}, } @phdthesis{6891, abstract = {While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. Cells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. Nevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. Therefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. The results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. Thus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. Thereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance. }, author = {Kopf, Aglaja}, isbn = {978-3-99078-002-2}, issn = {2663-337X}, keywords = {cell biology, immunology, leukocyte, migration, microfluidics}, pages = {171}, publisher = {Institute of Science and Technology Austria}, title = {{The implication of cytoskeletal dynamics on leukocyte migration}}, doi = {10.15479/AT:ISTA:6891}, year = {2019}, } @article{6328, abstract = {During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.}, author = {Renkawitz, Jörg and Kopf, Aglaja and Stopp, Julian A and de Vries, Ingrid and Driscoll, Meghan K. and Merrin, Jack and Hauschild, Robert and Welf, Erik S. and Danuser, Gaudenz and Fiolka, Reto and Sixt, Michael K}, journal = {Nature}, pages = {546--550}, publisher = {Springer Nature}, title = {{Nuclear positioning facilitates amoeboid migration along the path of least resistance}}, doi = {10.1038/s41586-019-1087-5}, volume = {568}, year = {2019}, } @article{6877, author = {Kopf, Aglaja and Sixt, Michael K}, issn = {1097-4172}, journal = {Cell}, number = {1}, pages = {51--53}, publisher = {Elsevier}, title = {{The neural crest pitches in to remove apoptotic debris}}, doi = {10.1016/j.cell.2019.08.047}, volume = {179}, year = {2019}, } @article{6830, author = {Contreras, Ximena and Hippenmeyer, Simon}, issn = {10974199}, journal = {Neuron}, number = {5}, pages = {750--752}, publisher = {Elsevier}, title = {{Memo1 tiles the radial glial cell grid}}, doi = {10.1016/j.neuron.2019.08.021}, volume = {103}, year = {2019}, } @article{6627, abstract = {Cortical microtubule arrays in elongating epidermal cells in both the root and stem of plants have the propensity of dynamic reorientations that are correlated with the activation or inhibition of growth. Factors regulating plant growth, among them the hormone auxin, have been recognized as regulators of microtubule array orientations. Some previous work in the field has aimed at elucidating the causal relationship between cell growth, the signaling of auxin or other growth-regulating factors, and microtubule array reorientations, with various conclusions. Here, we revisit this problem of causality with a comprehensive set of experiments in Arabidopsis thaliana, using the now available pharmacological and genetic tools. We use isolated, auxin-depleted hypocotyls, an experimental system allowing for full control of both growth and auxin signaling. We demonstrate that reorientation of microtubules is not directly triggered by an auxin signal during growth activation. Instead, reorientation is triggered by the activation of the growth process itself and is auxin-independent in its nature. We discuss these findings in the context of previous relevant work, including that on the mechanical regulation of microtubule array orientation.}, author = {Adamowski, Maciek and Li, Lanxin and Friml, Jiří}, issn = {1422-0067}, journal = {International Journal of Molecular Sciences}, number = {13}, publisher = {MDPI}, title = {{Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling}}, doi = {10.3390/ijms20133337}, volume = {20}, year = {2019}, } @article{7117, abstract = {We propose a novel generic shape optimization method for CAD models based on the eXtended Finite Element Method (XFEM). Our method works directly on the intersection between the model and a regular simulation grid, without the need to mesh or remesh, thus removing a bottleneck of classical shape optimization strategies. This is made possible by a novel hierarchical integration scheme that accurately integrates finite element quantities with sub-element precision. For optimization, we efficiently compute analytical shape derivatives of the entire framework, from model intersection to integration rule generation and XFEM simulation. Moreover, we describe a differentiable projection of shape parameters onto a constraint manifold spanned by user-specified shape preservation, consistency, and manufacturability constraints. We demonstrate the utility of our approach by optimizing mass distribution, strength-to-weight ratio, and inverse elastic shape design objectives directly on parameterized 3D CAD models.}, author = {Hafner, Christian and Schumacher, Christian and Knoop, Espen and Auzinger, Thomas and Bickel, Bernd and Bächer, Moritz}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {ACM}, title = {{X-CAD: Optimizing CAD Models with Extended Finite Elements}}, doi = {10.1145/3355089.3356576}, volume = {38}, year = {2019}, } @article{6189, abstract = {Suspended particles can alter the properties of fluids and in particular also affect the transition fromlaminar to turbulent flow. An earlier study [Mataset al.,Phys. Rev. Lett.90, 014501 (2003)] reported howthe subcritical (i.e., hysteretic) transition to turbulent puffs is affected by the addition of particles. Here weshow that in addition to this known transition, with increasing concentration a supercritical (i.e.,continuous) transition to a globally fluctuating state is found. At the same time the Newtonian-typetransition to puffs is delayed to larger Reynolds numbers. At even higher concentration only the globallyfluctuating state is found. The dynamics of particle laden flows are hence determined by two competinginstabilities that give rise to three flow regimes: Newtonian-type turbulence at low, a particle inducedglobally fluctuating state at high, and a coexistence state at intermediate concentrations.}, author = {Agrawal, Nishchal and Choueiri, George H and Hof, Björn}, issn = {10797114}, journal = {Physical Review Letters}, number = {11}, publisher = {American Physical Society}, title = {{Transition to turbulence in particle laden flows}}, doi = {10.1103/PhysRevLett.122.114502}, volume = {122}, year = {2019}, } @phdthesis{6371, abstract = {Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. i) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. ii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. iii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. iv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. We demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. }, author = {Igler, Claudia}, issn = {2663-337X}, keywords = {gene regulation, biophysics, transcription factor binding, bacteria}, pages = {152}, publisher = {Institute of Science and Technology Austria}, title = {{On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation}}, doi = {10.15479/AT:ISTA:6371}, year = {2019}, } @article{10286, abstract = {In this paper, we evaluate clock signals generated in ring oscillators and self-timed rings and the way their jitter can be transformed into random numbers. We show that counting the periods of the jittery clock signal produces random numbers of significantly better quality than the methods in which the jittery signal is simply sampled (the case in almost all current methods). Moreover, we use the counter values to characterize and continuously monitor the source of randomness. However, instead of using the widely used statistical variance, we propose to use Allan variance to do so. There are two main advantages: Allan variance is insensitive to low frequency noises such as flicker noise that are known to be autocorrelated and significantly less circuitry is required for its computation than that used to compute commonly used variance. We also show that it is essential to use a differential principle of randomness extraction from the jitter based on the use of two identical oscillators to avoid autocorrelations originating from external and internal global jitter sources and that this fact is valid for both kinds of rings. Last but not least, we propose a method of statistical testing based on high order Markov model to show the reduced dependencies when the proposed randomness extraction is applied.}, author = {Allini, Elie Noumon and Skórski, Maciej and Petura, Oto and Bernard, Florent and Laban, Marek and Fischer, Viktor}, issn = {2569-2925}, journal = {IACR Transactions on Cryptographic Hardware and Embedded Systems}, number = {3}, pages = {214--242}, publisher = {International Association for Cryptologic Research}, title = {{Evaluation and monitoring of free running oscillators serving as source of randomness}}, doi = {10.13154/tches.v2018.i3.214-242}, volume = {2018}, year = {2018}, } @article{10362, abstract = {Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.}, author = {Fisher, Patrick D. Ellis and Shen, Qi and Akpinar, Bernice and Davis, Luke K. and Chung, Kenny Kwok Hin and Baddeley, David and Šarić, Anđela and Melia, Thomas J. and Hoogenboom, Bart W. and Lin, Chenxiang and Lusk, C. Patrick}, issn = {1936-086X}, journal = {ACS Nano}, keywords = {general physics and astronomy}, number = {2}, pages = {1508--1518}, publisher = {American Chemical Society}, title = {{A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement}}, doi = {10.1021/acsnano.7b08044}, volume = {12}, year = {2018}, } @article{10360, abstract = {Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer’s disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.}, author = {Cohen, Samuel I. A. and Cukalevski, Risto and Michaels, Thomas C. T. and Šarić, Anđela and Törnquist, Mattias and Vendruscolo, Michele and Dobson, Christopher M. and Buell, Alexander K. and Knowles, Tuomas P. J. and Linse, Sara}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {523--531}, publisher = {Springer Nature}, title = {{Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide}}, doi = {10.1038/s41557-018-0023-x}, volume = {10}, year = {2018}, } @article{10357, abstract = {The misfolding and aggregation of proteins into linear fibrils is widespread in human biology, for example, in connection with amyloid formation and the pathology of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. The oligomeric species that are formed in the early stages of protein aggregation are of great interest, having been linked with the cellular toxicity associated with these conditions. However, these species are not characterized in any detail experimentally, and their properties are not well understood. Many of these species have been found to have approximately spherical morphology and to be held together by hydrophobic interactions. We present here an analytical statistical mechanical model of globular oligomer formation from simple idealized amphiphilic protein monomers and show that this correlates well with Monte Carlo simulations of oligomer formation. We identify the controlling parameters of the model, which are closely related to simple quantities that may be fitted directly from experiment. We predict that globular oligomers are unlikely to form at equilibrium in many polypeptide systems but instead form transiently in the early stages of amyloid formation. We contrast the globular model of oligomer formation to a well-established model of linear oligomer formation, highlighting how the differing ensemble properties of linear and globular oligomers offer a potential strategy for characterizing oligomers from experimental measurements.}, author = {Dear, Alexander J. and Šarić, Anđela and Michaels, Thomas C. T. and Dobson, Christopher M. and Knowles, Tuomas P. J.}, issn = {1520-5207}, journal = {The Journal of Physical Chemistry B}, keywords = {materials chemistry}, number = {49}, pages = {11721--11730}, publisher = {American Chemical Society}, title = {{Statistical mechanics of globular oligomer formation by protein molecules}}, doi = {10.1021/acs.jpcb.8b07805}, volume = {122}, year = {2018}, } @article{10359, abstract = {Biological membranes typically contain a large number of different components dispersed in small concentrations in the main membrane phase, including proteins, sugars, and lipids of varying geometrical properties. Most of these components do not bind the cargo. Here, we show that such “inert” components can be crucial for the precise control of cross-membrane trafficking. Using a statistical mechanics model and molecular dynamics simulations, we demonstrate that the presence of inert membrane components of small isotropic curvatures dramatically influences cargo endocytosis, even if the total spontaneous curvature of such a membrane remains unchanged. Curved lipids, such as cholesterol, as well as asymmetrically included proteins and tethered sugars can, therefore, actively participate in the control of the membrane trafficking of nanoscopic cargo. We find that even a low-level expression of curved inert membrane components can determine the membrane selectivity toward the cargo size and can be used to selectively target membranes of certain compositions. Our results suggest a robust and general method of controlling cargo trafficking by adjusting the membrane composition without needing to alter the concentration of receptors or the average membrane curvature. This study indicates that cells can prepare for any trafficking event by incorporating curved inert components in either of the membrane leaflets.}, author = {Curk, Tine and Wirnsberger, Peter and Dobnikar, Jure and Frenkel, Daan and Šarić, Anđela}, issn = {1530-6992}, journal = {Nano Letters}, keywords = {mechanical engineering, condensed matter physics}, number = {9}, pages = {5350--5356}, publisher = {American Chemical Society}, title = {{Controlling cargo trafficking in multicomponent membranes}}, doi = {10.1021/acs.nanolett.8b00786}, volume = {18}, year = {2018}, } @article{10358, abstract = {Probing reaction mechanisms of supramolecular processes in soft and biological matter, such as protein aggregation, is inherently challenging. This is because these processes involve multiple molecular mechanisms that are associated with the rearrangement of large numbers of weak bonds, resulting in complex free energy landscapes with many kinetic barriers. Reaction rate measurements at different temperatures can offer unprecedented insights into the underlying molecular mechanisms. However, to be able to interpret such measurements, a key challenge is to establish which properties of the complex free energy landscapes are probed by the reaction rate. Here, we present a reaction rate theory for supramolecular kinetics based on Kramers theory of diffusive reactions over multiple kinetic barriers. We find that reaction rates for protein aggregation are of the Arrhenius–Eyring type and that the associated activation energies probe only one relevant barrier along the respective free energy landscapes. We apply this advancement to interpret, in experiments and in coarse-grained computer simulations, reaction rates of amyloid aggregation in terms of molecular mechanisms and associated thermodynamic signatures. These results suggest a practical extension of the concept of rate-determining steps for complex supramolecular processes and establish a general platform for probing the underlying energy landscape using kinetic measurements.}, author = {Michaels, Thomas C. T. and Liu, Lucie X. and Curk, Samo and Bolhuis, Peter G. and Šarić, Anđela and Knowles, Tuomas P. J.}, issn = {1362-3028}, journal = {Molecular Physics}, keywords = {physical chemistry}, number = {21-22}, pages = {3055--3065}, publisher = {Taylor & Francis}, title = {{Reaction rate theory for supramolecular kinetics: application to protein aggregation}}, doi = {10.1080/00268976.2018.1474280}, volume = {116}, year = {2018}, } @article{10361, abstract = {Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular science, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical conditions such as Alzheimer's and Parkinson's diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss how ideas and concepts from chemical reaction kinetics can help to achieve this objective. In particular, we show how a combination of theory, experiments, and computer simulations, based on chemical kinetics, provides a general formalism for uncovering, at the molecular level, the mechanistic steps that underlie the phenomenon of amyloid fibril formation.}, author = {Michaels, Thomas C.T. and Šarić, Anđela and Habchi, Johnny and Chia, Sean and Meisl, Georg and Vendruscolo, Michele and Dobson, Christopher M. and Knowles, Tuomas P.J.}, issn = {1545-1593}, journal = {Annual Review of Physical Chemistry}, keywords = {physical and theoretical chemistry}, number = {1}, pages = {273--298}, publisher = {Annual Reviews}, title = {{Chemical kinetics for bridging molecular mechanisms and macroscopic measurements of amyloid fibril formation}}, doi = {10.1146/annurev-physchem-050317-021322}, volume = {69}, year = {2018}, } @article{10626, abstract = {Owing to their wide tunability, multiple internal degrees of freedom, and low disorder, graphene heterostructures are emerging as a promising experimental platform for fractional quantum Hall (FQH) studies. Here, we report FQH thermal activation gap measurements in dual graphite-gated monolayer graphene devices fabricated in an edgeless Corbino geometry. In devices with substrate-induced sublattice splitting, we find a tunable crossover between single- and multicomponent FQH states in the zero energy Landau level. Activation gaps in the single-component regime show excellent agreement with numerical calculations using a single broadening parameter Γ≈7.2K. In the first excited Landau level, in contrast, FQH gaps are strongly influenced by Landau level mixing, and we observe an unexpected valley-ordered state at integer filling ν=−4.}, author = {Polshyn, Hryhoriy and Zhou, H. and Spanton, E. M. and Taniguchi, T. and Watanabe, K. and Young, A. F.}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {22}, publisher = {American Physical Society}, title = {{Quantitative transport measurements of fractional quantum Hall energy gaps in edgeless graphene devices}}, doi = {10.1103/physrevlett.121.226801}, volume = {121}, year = {2018}, } @article{10627, abstract = {We present a scanning probe technique for measuring the dynamics of individual fluxoid transitions in multiply connected superconducting structures. In these measurements, a small magnetic particle attached to the tip of a silicon cantilever is scanned over a micron-size superconducting ring fabricated from a thin aluminum film. We find that near the superconducting transition temperature of the aluminum, the dissipation and frequency of the cantilever changes significantly at particular locations where the tip-induced magnetic flux penetrating the ring causes the two lowest-energy fluxoid states to become nearly degenerate. In this regime, we show that changes in the cantilever frequency and dissipation are well-described by a stochastic resonance (SR) process, wherein small oscillations of the cantilever in the presence of thermally activated phase slips (TAPS) in the ring give rise to a dynamical force that modifies the mechanical properties of the cantilever. Using the SR model, we calculate the average fluctuation rate of the TAPS as a function of temperature over a 32-dB range in frequency, and we compare it to the Langer-Ambegaokar-McCumber-Halperin theory for TAPS in one-dimensional superconducting structures.}, author = {Polshyn, Hryhoriy and Naibert, Tyler R. and Budakian, Raffi}, issn = {2469-9969}, journal = {Physical Review B}, number = {18}, publisher = {American Physical Society}, title = {{Imaging phase slip dynamics in micron-size superconducting rings}}, doi = {10.1103/physrevb.97.184501}, volume = {97}, year = {2018}, } @inproceedings{10883, abstract = {Solving parity games, which are equivalent to modal μ-calculus model checking, is a central algorithmic problem in formal methods, with applications in reactive synthesis, program repair, verification of branching-time properties, etc. Besides the standard compu- tation model with the explicit representation of games, another important theoretical model of computation is that of set-based symbolic algorithms. Set-based symbolic algorithms use basic set operations and one-step predecessor operations on the implicit description of games, rather than the explicit representation. The significance of symbolic algorithms is that they provide scalable algorithms for large finite-state systems, as well as for infinite-state systems with finite quotient. Consider parity games on graphs with n vertices and parity conditions with d priorities. While there is a rich literature of explicit algorithms for parity games, the main results for set-based symbolic algorithms are as follows: (a) the basic algorithm that requires O(nd) symbolic operations and O(d) symbolic space; and (b) an improved algorithm that requires O(nd/3+1) symbolic operations and O(n) symbolic space. In this work, our contributions are as follows: (1) We present a black-box set-based symbolic algorithm based on the explicit progress measure algorithm. Two important consequences of our algorithm are as follows: (a) a set-based symbolic algorithm for parity games that requires quasi-polynomially many symbolic operations and O(n) symbolic space; and (b) any future improvement in progress measure based explicit algorithms immediately imply an efficiency improvement in our set-based symbolic algorithm for parity games. (2) We present a set-based symbolic algorithm that requires quasi-polynomially many symbolic operations and O(d · log n) symbolic space. Moreover, for the important special case of d ≤ log n, our algorithm requires only polynomially many symbolic operations and poly-logarithmic symbolic space.}, author = {Chatterjee, Krishnendu and Dvořák, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {22nd International Conference on Logic for Programming, Artificial Intelligence and Reasoning}, issn = {2398-7340}, location = {Awassa, Ethiopia}, pages = {233--253}, publisher = {EasyChair}, title = {{Quasipolynomial set-based symbolic algorithms for parity games}}, doi = {10.29007/5z5k}, volume = {57}, year = {2018}, } @article{1092, abstract = {A graphical model encodes conditional independence relations via the Markov properties. For an undirected graph these conditional independence relations can be represented by a simple polytope known as the graph associahedron, which can be constructed as a Minkowski sum of standard simplices. We show that there is an analogous polytope for conditional independence relations coming from a regular Gaussian model, and it can be defined using multiinformation or relative entropy. For directed acyclic graphical models we give a construction of this polytope as a Minkowski sum of matroid polytopes. Finally, we apply this geometric insight to construct a new ordering-based search algorithm for causal inference via directed acyclic graphical models. }, author = {Mohammadi, Fatemeh and Uhler, Caroline and Wang, Charles and Yu, Josephine}, journal = {SIAM Journal on Discrete Mathematics}, number = {1}, pages = {64--93}, publisher = {SIAM}, title = {{Generalized permutohedra from probabilistic graphical models}}, doi = {10.1137/16M107894X}, volume = {32}, year = {2018}, } @inproceedings{11, abstract = {We report on a novel strategy to derive mean-field limits of quantum mechanical systems in which a large number of particles weakly couple to a second-quantized radiation field. The technique combines the method of counting and the coherent state approach to study the growth of the correlations among the particles and in the radiation field. As an instructional example, we derive the Schrödinger–Klein–Gordon system of equations from the Nelson model with ultraviolet cutoff and possibly massless scalar field. In particular, we prove the convergence of the reduced density matrices (of the nonrelativistic particles and the field bosons) associated with the exact time evolution to the projectors onto the solutions of the Schrödinger–Klein–Gordon equations in trace norm. Furthermore, we derive explicit bounds on the rate of convergence of the one-particle reduced density matrix of the nonrelativistic particles in Sobolev norm.}, author = {Leopold, Nikolai K and Pickl, Peter}, location = {Munich, Germany}, pages = {185 -- 214}, publisher = {Springer}, title = {{Mean-field limits of particles in interaction with quantised radiation fields}}, doi = {10.1007/978-3-030-01602-9_9}, volume = {270}, year = {2018}, } @article{11063, abstract = {The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear envelope remain unclear. Here, we report that depletion of the NPC basket protein Tpr, but not Nup153, dramatically increases the total NPC number in various cell types. This negative regulation of Tpr occurs via a phosphorylation cascade of extracellular signal-regulated kinase (ERK), the central kinase of the mitogen-activated protein kinase (MAPK) pathway. Tpr serves as a scaffold for ERK to phosphorylate the nucleoporin (Nup) Nup153, which is critical for early stages of NPC biogenesis. Our results reveal a critical role of the Nup Tpr in coordinating signal transduction pathways during cell proliferation and the dynamic organization of the nucleus.}, author = {McCloskey, Asako and Ibarra, Arkaitz and HETZER, Martin W}, issn = {0890-9369}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {19-20}, pages = {1321--1331}, publisher = {Cold Spring Harbor Laboratory}, title = {{Tpr regulates the total number of nuclear pore complexes per cell nucleus}}, doi = {10.1101/gad.315523.118}, volume = {32}, year = {2018}, } @article{11064, abstract = {Biomarkers of aging can be used to assess the health of individuals and to study aging and age-related diseases. We generate a large dataset of genome-wide RNA-seq profiles of human dermal fibroblasts from 133 people aged 1 to 94 years old to test whether signatures of aging are encoded within the transcriptome. We develop an ensemble machine learning method that predicts age to a median error of 4 years, outperforming previous methods used to predict age. The ensemble was further validated by testing it on ten progeria patients, and our method is the only one that predicts accelerated aging in these patients.}, author = {Fleischer, Jason G. and Schulte, Roberta and Tsai, Hsiao H. and Tyagi, Swati and Ibarra, Arkaitz and Shokhirev, Maxim N. and Huang, Ling and HETZER, Martin W and Navlakha, Saket}, issn = {1474-760X}, journal = {Genome Biology}, publisher = {BioMed Central}, title = {{Predicting age from the transcriptome of human dermal fibroblasts}}, doi = {10.1186/s13059-018-1599-6}, volume = {19}, year = {2018}, } @article{11508, abstract = {Distant luminous Lyman-α emitters (LAEs) are excellent targets for spectroscopic observations of galaxies in the epoch of reionisation (EoR). We present deep high-resolution (R = 5000) VLT/X-shooter observations, along with an extensive collection of photometric data of COLA1, a proposed double peaked LAE at z = 6.6. We rule out the possibility that COLA1’s emission line is an [OII] doublet at z = 1.475 on the basis of i) the asymmetric red line-profile and flux ratio of the peaks (blue/red=0.31 ± 0.03) and ii) an unphysical [OII]/Hα ratio ([OII]/Hα >  22). We show that COLA1’s observed B-band flux is explained by a faint extended foreground LAE, for which we detect Lyα and [OIII] at z = 2.142. We thus conclude that COLA1 is a real double-peaked LAE at z = 6.593, the first discovered at z >  6. COLA1 is UV luminous (M1500 = −21.6 ± 0.3), has a high equivalent width (EW0,Lyα = 120−40+50 Å) and very compact Lyα emission (r50,Lyα = 0.33−0.04+0.07 kpc). Relatively weak inferred Hβ+[OIII] line-emission from Spitzer/IRAC indicates an extremely low metallicity of Z <  1/20 Z⊙ or reduced strength of nebular lines due to high escape of ionising photons. The small Lyα peak separation of 220 ± 20 km s−1 implies a low HI column density and an ionising photon escape fraction of ≈15 − 30%, providing the first direct evidence that such galaxies contribute actively to the reionisation of the Universe at z >  6. Based on simple estimates, we find that COLA1 could have provided just enough photons to reionise its own ≈0.3 pMpc (2.3 cMpc) bubble, allowing the blue Lyα line to be observed. However, we also discuss alternative scenarios explaining the detected double peaked nature of COLA1. Our results show that future high-resolution observations of statistical samples of double peaked LAEs at z >  5 are a promising probe of the occurrence of ionised regions around galaxies in the EoR.}, author = {Matthee, Jorryt J and Sobral, David and Gronke, Max and Paulino-Afonso, Ana and Stefanon, Mauro and Röttgering, Huub}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: high-redshift / galaxies: formation / dark ages / reionization / first stars / techniques: spectroscopic / intergalactic medium}, publisher = {EDP Sciences}, title = {{Confirmation of double peaked Lyα emission at z = 6.593: Witnessing a galaxy directly contributing to the reionisation of the universe}}, doi = {10.1051/0004-6361/201833528}, volume = {619}, year = {2018}, } @article{11549, abstract = {We investigate the clustering properties of ∼7000 H β + [O III] and [O II] narrowband-selected emitters at z ∼ 0.8–4.7 from the High-z Emission Line Survey. We find clustering lengths, r0, of 1.5–4.0 h−1 Mpc and minimum dark matter halo masses of 1010.7–12.1 M⊙ for our z = 0.8–3.2 H β + [O III] emitters and r0 ∼ 2.0–8.3 h−1 Mpc and halo masses of 1011.5–12.6 M⊙ for our z = 1.5–4.7 [O II] emitters. We find r0 to strongly increase both with increasing line luminosity and redshift. By taking into account the evolution of the characteristic line luminosity, L⋆(z), and using our model predictions of halo mass given r0, we find a strong, redshift-independent increasing trend between L/L⋆(z) and minimum halo mass. The faintest H β + [O III] emitters are found to reside in 109.5 M⊙ haloes and the brightest emitters in 1013.0 M⊙ haloes. For [O II] emitters, the faintest emitters are found in 1010.5 M⊙ haloes and the brightest emitters in 1012.6 M⊙ haloes. A redshift-independent stellar mass dependency is also observed where the halo mass increases from 1011 to 1012.5 M⊙ for stellar masses of 108.5 to 1011.5 M⊙, respectively. We investigate the interdependencies of these trends by repeating our analysis in a Lline−Mstar grid space for our most populated samples (H β + [O III] z = 0.84 and [O II] z = 1.47) and find that the line luminosity dependency is stronger than the stellar mass dependency on halo mass. For L > L⋆ emitters at all epochs, we find a relatively flat trend with halo masses of 1012.5–13 M⊙, which may be due to quenching mechanisms in massive haloes that is consistent with a transitional halo mass predicted by models.}, author = {Khostovan, A A and Sobral, D and Mobasher, B and Best, P N and Smail, I and Matthee, Jorryt J and Darvish, B and Nayyeri, H and Hemmati, S and Stott, J P}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: haloes, galaxies: high-redshift, galaxies: star formation, cosmology: observations, large-scale structure of Universe}, number = {3}, pages = {2999--3015}, publisher = {Oxford University Press}, title = {{The clustering of H β + [O III] and [O II] emitters since z ∼ 5: Dependencies with line luminosity and stellar mass}}, doi = {10.1093/mnras/sty925}, volume = {478}, year = {2018}, } @article{11557, abstract = {Deep narrow-band surveys have revealed a large population of faint Ly α emitters (LAEs) in the distant Universe, but relatively little is known about the most luminous sources (⁠LLyα≳1042.7 erg s−1; LLyα≳L∗Lyα⁠). Here we present the spectroscopic follow-up of 21 luminous LAEs at z ∼ 2–3 found with panoramic narrow-band surveys over five independent extragalactic fields (≈4 × 106 Mpc3 surveyed at z ∼ 2.2 and z ∼ 3.1). We use WHT/ISIS, Keck/DEIMOS, and VLT/X-SHOOTER to study these sources using high ionization UV lines. Luminous LAEs at z ∼ 2–3 have blue UV slopes (⁠β=−2.0+0.3−0.1⁠) and high Ly α escape fractions (⁠50+20−15 per cent) and span five orders of magnitude in UV luminosity (MUV ≈ −19 to −24). Many (70 per cent) show at least one high ionization rest-frame UV line such as C IV, N V, C III], He II or O III], typically blue-shifted by ≈100–200 km s−1 relative to Ly α. Their Ly α profiles reveal a wide variety of shapes, including significant blue-shifted components and widths from 200 to 4000 km s−1. Overall, 60 ± 11  per cent appear to be active galactic nucleus (AGN) dominated, and at LLyα > 1043.3 erg s−1 and/or MUV < −21.5 virtually all LAEs are AGNs with high ionization parameters (log U = 0.6 ± 0.5) and with metallicities of ≈0.5 − 1 Z⊙. Those lacking signatures of AGNs (40 ± 11  per cent) have lower ionization parameters (⁠logU=−3.0+1.6−0.9 and log ξion = 25.4 ± 0.2) and are apparently metal-poor sources likely powered by young, dust-poor ‘maximal’ starbursts. Our results show that luminous LAEs at z ∼ 2–3 are a diverse population and that 2×L∗Lyα and 2×M∗UV mark a sharp transition in the nature of LAEs, from star formation dominated to AGN dominated.}, author = {Sobral, David and Matthee, Jorryt J and Darvish, Behnam and Smail, Ian and Best, Philip N and Alegre, Lara and Röttgering, Huub and Mobasher, Bahram and Paulino-Afonso, Ana and Stroe, Andra and Oteo, Iván}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: active, galaxies: evolution, galaxies: high-redshift, galaxies: ISM, galaxies: starburst, cosmology: observations}, number = {2}, pages = {2817--2840}, publisher = {Oxford University Press}, title = {{The nature of luminous Ly α emitters at z ∼ 2–3: Maximal dust-poor starbursts and highly ionizing AGN}}, doi = {10.1093/mnras/sty782}, volume = {477}, year = {2018}, } @article{11558, abstract = {We present and explore deep narrow- and medium-band data obtained with the Subaru and the Isaac Newton Telescopes in the ∼2 deg2 COSMOS field. We use these data as an extremely wide, low-resolution (R ∼ 20–80) Integral Field Unit survey to slice through the COSMOS field and obtain a large sample of ∼4000 Ly α emitters (LAEs) from z ∼ 2 to 6 in 16 redshift slices (SC4K). We present new Ly α luminosity functions (LFs) covering a comoving volume of ∼108 Mpc3. SC4K extensively complements ultradeep surveys, jointly covering over 4 dex in Ly α luminosity and revealing a global (2.5 < z < 6) synergy LF with α=−1.93+0.12−0.12⁠, log10Φ∗Lyα=−3.45+0.22−0.29 Mpc−3, and log10L∗Lyα=42.93+0.15−0.11 erg s−1. The Schechter component of the Ly α LF reveals a factor ∼5 rise in L∗Lyα and a ∼7 × decline in Φ∗Lyα from z ∼ 2 to 6. The data reveal an extra power-law (or Schechter) component above LLy α ≈ 1043.3 erg s−1 at z ∼ 2.2–3.5 and we show that it is partially driven by X-ray and radio active galactic nucleus (AGN), as their Ly α LF resembles the excess. The power-law component vanishes and/or is below our detection limits above z > 3.5, likely linked with the evolution of the AGN population. The Ly α luminosity density rises by a factor ∼2 from z ∼ 2 to 3 but is then found to be roughly constant (⁠1.1+0.2−0.2×1040 erg s−1 Mpc−3) to z ∼ 6, despite the ∼0.7 dex drop in ultraviolet (UV) luminosity density. The Ly α/UV luminosity density ratio rises from 4 ± 1 per cent to 30 ± 6 per cent from z ∼ 2.2 to 6. Our results imply a rise of a factor of ≈2 in the global ionization efficiency (ξion) and a factor ≈4 ± 1 in the Ly α escape fraction from z ∼ 2 to 6, hinting for evolution in both the typical burstiness/stellar populations and even more so in the typical interstellar medium conditions allowing Ly α photons to escape.}, author = {Sobral, David and Santos, Sérgio and Matthee, Jorryt J and Paulino-Afonso, Ana and Ribeiro, Bruno and Calhau, João and Khostovan, Ali A}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: formation, galaxies: high-redshift, galaxies: luminosity function, mass function, galaxies: statistics}, number = {4}, pages = {4725--4752}, publisher = {Oxford University Press}, title = {{Slicing COSMOS with SC4K: The evolution of typical Ly α emitters and the Ly α escape fraction from z ∼ 2 to 6}}, doi = {10.1093/mnras/sty378}, volume = {476}, year = {2018}, } @article{11555, abstract = {We investigate the morphology of the [C II] emission in a sample of ‘normal’ star-forming galaxies at 5 < z < 7.2 in relation to their UV (rest-frame) counterpart. We use new Atacama Large Millimetre/submillimetre Array (ALMA) observations of galaxies at z ∼ 6–7, as well as a careful re-analysis of archival ALMA data. In total 29 galaxies were analysed, 21 of which are detected in [C II]. For several of the latter the [C II] emission breaks into multiple components. Only a fraction of these [C II] components, if any, is associated with the primary UV systems, while the bulk of the [C II] emission is associated either with fainter UV components, or not associated with any UV counterpart at the current limits. By taking into account the presence of all these components, we find that the L[CII]–SFR (star formation rate) relation at early epochs is fully consistent with the local relation, but it has a dispersion of 0.48 ± 0.07 dex, which is about two times larger than observed locally. We also find that the deviation from the local L[CII]–SFR relation has a weak anticorrelation with the EW(Ly α). The morphological analysis also reveals that [C II] emission is generally much more extended than the UV emission. As a consequence, these primordial galaxies are characterized by a [C II] surface brightness generally much lower than expected from the local Σ[CII]−ΣSFR relation. These properties are likely a consequence of a combination of different effects, namely gas metallicity, [C II] emission from obscured star-forming regions, strong variations of the ionization parameter, and circumgalactic gas in accretion or ejected by these primeval galaxies.}, author = {Carniani, S and Maiolino, R and Amorin, R and Pentericci, L and Pallottini, A and Ferrara, A and Willott, C J and Smit, R and Matthee, Jorryt J and Sobral, D and Santini, P and Castellano, M and De Barros, S and Fontana, A and Grazian, A and Guaita, L}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: high-redshift, galaxies: ISM, galaxies: formation}, number = {1}, pages = {1170--1184}, publisher = {Oxford University Press}, title = {{Kiloparsec-scale gaseous clumps and star formation at z = 5–7}}, doi = {10.1093/mnras/sty1088}, volume = {478}, year = {2018}, } @article{11584, abstract = {Observations show that star-forming galaxies reside on a tight 3D plane between mass, gas-phase metallicity, and star formation rate (SFR), which can be explained by the interplay between metal-poor gas inflows, SFR and outflows. However, different metals are released on different time-scales, which may affect the slope of this relation. Here, we use central, star-forming galaxies with Mstar = 109.0–10.5 M⊙ from the EAGLE hydrodynamical simulation to examine 3D relations between mass, SFR, and chemical enrichment using absolute and relative C, N, O, and Fe abundances. We show that the scatter is smaller when gas-phase α-enhancement is used rather than metallicity. A similar plane also exists for stellar α-enhancement, implying that present-day specific SFRs are correlated with long time-scale star formation histories. Between z = 0 and 1, the α-enhancement plane is even more insensitive to redshift than the plane using metallicity. However, it evolves at z > 1 due to lagging iron yields. At fixed mass, galaxies with higher SFRs have star formation histories shifted towards late times, are more α-enhanced, and this α-enhancement increases with redshift as observed. These findings suggest that relations between physical properties inferred from observations may be affected by systematic variations in α-enhancements.}, author = {Matthee, Jorryt J and Schaye, Joop}, issn = {1745-3933}, journal = {Monthly Notices of the Royal Astronomical Society: Letters}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: abundances, galaxies: evolution, galaxies: formation, galaxies: star formation}, number = {1}, pages = {L34 -- L39}, publisher = {Oxford University Press}, title = {{Star-forming galaxies are predicted to lie on a fundamental plane of mass, star formation rate, and α-enhancement}}, doi = {10.1093/mnrasl/sly093}, volume = {479}, year = {2018}, } @article{11619, abstract = {We report on the confirmation and mass determination of π Men c, the first transiting planet discovered by NASA’s TESS space mission. π Men is a naked-eye (V = 5.65 mag), quiet G0 V star that was previously known to host a sub-stellar companion (π Men b) on a longperiod (Porb = 2091 days), eccentric (e = 0.64) orbit. Using TESS time-series photometry, combined with Gaia data, published UCLES at AAT Doppler measurements, and archival HARPS at ESO-3.6m radial velocities, we found that π Men c is a close-in planet with an orbital period of Porb = 6.27 days, a mass of Mc = 4.52 ± 0.81 M⊕, and a radius of Rc = 2.06 ± 0.03 R⊕. Based on the planet’s orbital period and size, π Men c is a super-Earth located at, or close to, the radius gap, while its mass and bulk density suggest it may have held on to a significant atmosphere. Because of the brightness of the host star, this system is highly suitable for a wide range of further studies to characterize the planetary atmosphere and dynamical properties. We also performed an asteroseismic analysis of the TESS data and detected a hint of power excess consistent with the seismic values expected for this star, although this result depends on the photometric aperture used to extract the light curve. This marginal detection is expected from pre-launch simulations hinting at the asteroseismic potential of the TESS mission for longer, multi-sector observations and/or for more evolved bright stars.}, author = {Gandolfi, D. and Barragán, O. and Livingston, J. H. and Fridlund, M. and Justesen, A. B. and Redfield, S. and Fossati, L. and Mathur, S. and Grziwa, S. and Cabrera, J. and García, R. A. and Persson, C. M. and Van Eylen, V. and Hatzes, A. P. and Hidalgo, D. and Albrecht, S. and Bugnet, Lisa Annabelle and Cochran, W. D. and Csizmadia, Sz. and Deeg, H. and Eigmüller, Ph. and Endl, M. and Erikson, A. and Esposito, M. and Guenther, E. and Korth, J. and Luque, R. and Montañes Rodríguez, P. and Nespral, D. and Nowak, G. and Pätzold, M. and Prieto-Arranz, J.}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, planetary systems / planets and satellites, detection / planets and satellites, fundamental parameters / planets and satellites, terrestrial planets / stars, fundamental parameters}, publisher = {EDP Sciences}, title = {{TESS’s first planet: A super-Earth transiting the naked-eye star π Mensae}}, doi = {10.1051/0004-6361/201834289}, volume = {619}, year = {2018}, } @article{11618, abstract = {Asteroseismology provides global stellar parameters such as masses, radii, or surface gravities using mean global seismic parameters and effective temperature for thousands of low-mass stars (0.8 M⊙ < M < 3 M⊙). This methodology has been successfully applied to stars in which acoustic modes excited by turbulent convection are measured. Other methods such as the Flicker technique can also be used to determine stellar surface gravities, but only works for log g above 2.5 dex. In this work, we present a new metric called FliPer (Flicker in spectral power density, in opposition to the standard Flicker measurement which is computed in the time domain); it is able to extend the range for which reliable surface gravities can be obtained (0.1 < log g < 4.6 dex) without performing any seismic analysis for stars brighter than Kp < 14. FliPer takes into account the average variability of a star measured in the power density spectrum in a given range of frequencies. However, FliPer values calculated on several ranges of frequency are required to better characterize a star. Using a large set of asteroseismic targets it is possible to calibrate the behavior of surface gravity with FliPer through machine learning. This calibration made with a random forest regressor covers a wide range of surface gravities from main-sequence stars to subgiants and red giants, with very small uncertainties from 0.04 to 0.1 dex. FliPer values can be inserted in automatic global seismic pipelines to either give an estimation of the stellar surface gravity or to assess the quality of the seismic results by detecting any outliers in the obtained νmax values. FliPer also constrains the surface gravities of main-sequence dwarfs using only long-cadence data for which the Nyquist frequency is too low to measure the acoustic-mode properties.}, author = {Bugnet, Lisa Annabelle and García, R. A. and Davies, G. R. and Mathur, S. and Corsaro, E. and Hall, O. J. and Rendle, B. M.}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, asteroseismology / methods, data analysis / stars, oscillations}, publisher = {EDP Sciences}, title = {{FliPer: A global measure of power density to estimate surface gravities of main-sequence solar-like stars and red giants}}, doi = {10.1051/0004-6361/201833106}, volume = {620}, year = {2018}, } @article{11620, abstract = {We report the discovery and characterization of HD 89345b (K2-234b; EPIC 248777106b), a Saturn-sized planet orbiting a slightly evolved star. HD 89345 is a bright star (V = 9.3 mag) observed by the K2 mission with 1 min time sampling. It exhibits solar-like oscillations. We conducted asteroseismology to determine the parameters of the star, finding the mass and radius to be 1.12+0.04−0.01M⊙ and 1.657+0.020−0.004R⊙⁠, respectively. The star appears to have recently left the main sequence, based on the inferred age, 9.4+0.4−1.3Gyr⁠, and the non-detection of mixed modes. The star hosts a ‘warm Saturn’ (P = 11.8 d, Rp = 6.86 ± 0.14 R⊕). Radial-velocity follow-up observations performed with the FIbre-fed Echelle Spectrograph, HARPS, and HARPS-N spectrographs show that the planet has a mass of 35.7 ± 3.3 M⊕. The data also show that the planet’s orbit is eccentric (e ≈ 0.2). An investigation of the rotational splitting of the oscillation frequencies of the star yields no conclusive evidence on the stellar inclination angle. We further obtained Rossiter–McLaughlin observations, which result in a broad posterior of the stellar obliquity. The planet seems to confirm to the same patterns that have been observed for other sub-Saturns regarding planet mass and multiplicity, orbital eccentricity, and stellar metallicity.}, author = {Van Eylen, V and Dai, F and Mathur, S and Gandolfi, D and Albrecht, S and Fridlund, M and García, R A and Guenther, E and Hjorth, M and Justesen, A B and Livingston, J and Lund, M N and Pérez Hernández, F and Prieto-Arranz, J and Regulo, C and Bugnet, Lisa Annabelle and Everett, M E and Hirano, T and Nespral, D and Nowak, G and Palle, E and Silva Aguirre, V and Trifonov, T and Winn, J N and Barragán, O and Beck, P G and Chaplin, W J and Cochran, W D and Csizmadia, S and Deeg, H and Endl, M and Heeren, P and Grziwa, S and Hatzes, A P and Hidalgo, D and Korth, J and Mathis, S and Montañes Rodriguez, P and Narita, N and Patzold, M and Persson, C M and Rodler, F and Smith, A M S}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, asteroseismology, planets and satellites: composition, planets and satellites: formation, planets and satellites: fundamental parameters}, number = {4}, pages = {4866--4880}, publisher = {Oxford University Press}, title = {{HD 89345: A bright oscillating star hosting a transiting warm Saturn-sized planet observed by K2}}, doi = {10.1093/mnras/sty1390}, volume = {478}, year = {2018}, } @unpublished{11631, abstract = {The recently launched NASA Transiting Exoplanet Survey Satellite (TESS) mission is going to collect lightcurves for a few hundred million of stars and we expect to increase the number of pulsating stars to analyze compared to the few thousand stars observed by the CoRoT, Kepler and K2 missions. However, most of the TESS targets have not yet been properly classified and characterized. In order to improve the analysis of the TESS data, it is crucial to determine the type of stellar pulsations in a timely manner. We propose an automatic method to classify stars attending to their pulsation properties, in particular, to identify solar-like pulsators among all TESS targets. It relies on the use of the global amount of power contained in the power spectrum (already known as the FliPer method) as a key parameter, along with the effective temperature, to feed into a machine learning classifier. Our study, based on TESS simulated datasets, shows that we are able to classify pulsators with a 98% accuracy.}, author = {Bugnet, Lisa Annabelle and García, R. A. and Davies, G. R. and Mathur, S. and Hall, O. J. and Rendle, B. M.}, booktitle = {arXiv}, keywords = {asteroseismology - methods, data analysis - stars, oscillations}, title = {{FliPer: Classifying TESS pulsating stars}}, doi = {10.48550/arXiv.1811.12140}, year = {2018}, } @article{11657, abstract = {The minimum cut problem for an undirected edge-weighted graph asks us to divide its set of nodes into two blocks while minimizing the weight sum of the cut edges. Here, we introduce a linear-time algorithm to compute near-minimum cuts. Our algorithm is based on cluster contraction using label propagation and Padberg and Rinaldi’s contraction heuristics [SIAM Review, 1991]. We give both sequential and shared-memory parallel implementations of our algorithm. Extensive experiments on both real-world and generated instances show that our algorithm finds the optimal cut on nearly all instances significantly faster than other state-of-the-art exact algorithms, and our error rate is lower than that of other heuristic algorithms. In addition, our parallel algorithm runs a factor 7.5× faster on average when using 32 threads. To further speed up computations, we also give a version of our algorithm that performs random edge contractions as preprocessing. This version achieves a lower running time and better parallel scalability at the expense of a higher error rate.}, author = {Henzinger, Monika H and Noe, Alexander and Schulz, Christian and Strash, Darren}, issn = {1084-6654}, journal = {ACM Journal of Experimental Algorithmics}, keywords = {Theoretical Computer Science}, pages = {1--22}, publisher = {Association for Computing Machinery}, title = {{Practical minimum cut algorithms}}, doi = {10.1145/3274662}, volume = {23}, year = {2018}, } @article{11667, abstract = {The focus of classic mechanism design has been on truthful direct-revelation mechanisms. In the context of combinatorial auctions, the truthful direct-revelation mechanism that maximizes social welfare is the Vickrey-Clarke-Groves mechanism. For many valuation spaces, computing the allocation and payments of the VCG mechanism, however, is a computationally hard problem. We thus study the performance of the VCG mechanism when bidders are forced to choose bids from a subspace of the valuation space for which the VCG outcome can be computed efficiently. We prove improved upper bounds on the welfare loss for restrictions to additive bids and upper and lower bounds for restrictions to non-additive bids. These bounds show that increased expressiveness can give rise to additional equilibria of poorer efficiency.}, author = {Dütting, Paul and Henzinger, Monika H and Starnberger, Martin}, issn = {2167-8383}, journal = {ACM Transactions on Economics and Computation}, keywords = {Theory of computation, Algorithmic game theory and mechanism design, Applied computing, Economics, Simplified mechanisms, Combinatorial auctions with item bidding, Price of anarchy}, number = {2}, publisher = {Association for Computing Machinery}, title = {{Valuation compressions in VCG-based combinatorial auctions}}, doi = {10.1145/3232860}, volume = {6}, year = {2018}, } @article{11664, abstract = {We present a deterministic incremental algorithm for exactly maintaining the size of a minimum cut with O(log3 n log log2 n) amortized time per edge insertion and O(1) query time. This result partially answers an open question posed by Thorup (2007). It also stays in sharp contrast to a polynomial conditional lower bound for the fully dynamic weighted minimum cut problem. Our algorithm is obtained by combining a sparsification technique of Kawarabayashi and Thorup (2015) or its recent improvement by Henzinger, Rao, and Wang (2017), and an exact incremental algorithm of Henzinger (1997). We also study space-efficient incremental algorithms for the minimum cut problem. Concretely, we show that there exists an O(nlog n/ε2) space Monte Carlo algorithm that can process a stream of edge insertions starting from an empty graph, and with high probability, the algorithm maintains a (1+ε)-approximation to the minimum cut. The algorithm has O((α (n) log3 n)/ε 2) amortized update time and constant query time, where α (n) stands for the inverse of Ackermann function.}, author = {Goranci, Gramoz and Henzinger, Monika H and Thorup, Mikkel}, issn = {1549-6333}, journal = {ACM Transactions on Algorithms}, number = {2}, publisher = {Association for Computing Machinery}, title = {{Incremental exact min-cut in polylogarithmic amortized update time}}, doi = {10.1145/3174803}, volume = {14}, year = {2018}, } @article{11757, abstract = {We develop a dynamic version of the primal-dual method for optimization problems, and apply it to obtain the following results. (1) For the dynamic set-cover problem, we maintain an O ( f 2)-approximately optimal solution in O ( f · log(m + n)) amortized update time, where f is the maximum “frequency” of an element, n is the number of sets, and m is the maximum number of elements in the universe at any point in time. (2) For the dynamic b-matching problem, we maintain an O (1)-approximately optimal solution in O (log3 n) amortized update time, where n is the number of nodes in the graph.}, author = {Bhattacharya, Sayan and Henzinger, Monika H and Italiano, Giuseppe}, issn = {0890-5401}, journal = {Information and Computation}, number = {08}, pages = {219--239}, publisher = {Elsevier}, title = {{Dynamic algorithms via the primal-dual method}}, doi = {10.1016/j.ic.2018.02.005}, volume = {261}, year = {2018}, } @inproceedings{11828, abstract = {We consider the problem of dynamically maintaining (approximate) all-pairs effective resistances in separable graphs, which are those that admit an n^{c}-separator theorem for some c<1. We give a fully dynamic algorithm that maintains (1+epsilon)-approximations of the all-pairs effective resistances of an n-vertex graph G undergoing edge insertions and deletions with O~(sqrt{n}/epsilon^2) worst-case update time and O~(sqrt{n}/epsilon^2) worst-case query time, if G is guaranteed to be sqrt{n}-separable (i.e., it is taken from a class satisfying a sqrt{n}-separator theorem) and its separator can be computed in O~(n) time. Our algorithm is built upon a dynamic algorithm for maintaining approximate Schur complement that approximately preserves pairwise effective resistances among a set of terminals for separable graphs, which might be of independent interest. We complement our result by proving that for any two fixed vertices s and t, no incremental or decremental algorithm can maintain the s-t effective resistance for sqrt{n}-separable graphs with worst-case update time O(n^{1/2-delta}) and query time O(n^{1-delta}) for any delta>0, unless the Online Matrix Vector Multiplication (OMv) conjecture is false. We further show that for general graphs, no incremental or decremental algorithm can maintain the s-t effective resistance problem with worst-case update time O(n^{1-delta}) and query-time O(n^{2-delta}) for any delta >0, unless the OMv conjecture is false.}, author = {Goranci, Gramoz and Henzinger, Monika H and Peng, Pan}, booktitle = {26th Annual European Symposium on Algorithms}, isbn = {9783959770811}, issn = {1868-8969}, location = {Helsinki, Finland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Dynamic effective resistances and approximate schur complement on separable graphs}}, doi = {10.4230/LIPICS.ESA.2018.40}, volume = {112}, year = {2018}, } @inproceedings{11827, abstract = {We study the metric facility location problem with client insertions and deletions. This setting differs from the classic dynamic facility location problem, where the set of clients remains the same, but the metric space can change over time. We show a deterministic algorithm that maintains a constant factor approximation to the optimal solution in worst-case time O~(2^{O(kappa^2)}) per client insertion or deletion in metric spaces while answering queries about the cost in O(1) time, where kappa denotes the doubling dimension of the metric. For metric spaces with bounded doubling dimension, the update time is polylogarithmic in the parameters of the problem.}, author = {Goranci, Gramoz and Henzinger, Monika H and Leniowski, Dariusz}, booktitle = {26th Annual European Symposium on Algorithms}, isbn = {9783959770811}, issn = {1868-8969}, location = {Helsinki, Finland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{A tree structure for dynamic facility location}}, doi = {10.4230/LIPICS.ESA.2018.39}, volume = {112}, year = {2018}, } @article{11768, abstract = {In the decremental single-source shortest paths (SSSP) problem, we want to maintain the distances between a given source node s and every other node in an n-node m-edge graph G undergoing edge deletions. While its static counterpart can be solved in near-linear time, this decremental problem is much more challenging even in the undirected unweighted case. In this case, the classic O(mn) total update time of Even and Shiloach [16] has been the fastest known algorithm for three decades. At the cost of a (1+ϵ)-approximation factor, the running time was recently improved to n2+o(1) by Bernstein and Roditty [9]. In this article, we bring the running time down to near-linear: We give a (1+ϵ)-approximation algorithm with m1+o(1) expected total update time, thus obtaining near-linear time. Moreover, we obtain m1+o(1) log W time for the weighted case, where the edge weights are integers from 1 to W. The only prior work on weighted graphs in o(mn) time is the mn0.9 + o(1)-time algorithm by Henzinger et al. [18, 19], which works for directed graphs with quasi-polynomial edge weights. The expected running time bound of our algorithm holds against an oblivious adversary. In contrast to the previous results, which rely on maintaining a sparse emulator, our algorithm relies on maintaining a so-called sparse (h, ϵ)-hop set introduced by Cohen [12] in the PRAM literature. An (h, ϵ)-hop set of a graph G=(V, E) is a set F of weighted edges such that the distance between any pair of nodes in G can be (1+ϵ)-approximated by their h-hop distance (given by a path containing at most h edges) on G′=(V, E ∪ F). Our algorithm can maintain an (no(1), ϵ)-hop set of near-linear size in near-linear time under edge deletions. It is the first of its kind to the best of our knowledge. To maintain approximate distances using this hop set, we extend the monotone Even-Shiloach tree of Henzinger et al. [20] and combine it with the bounded-hop SSSP technique of Bernstein [4, 5] and Mądry [27]. These two new tools might be of independent interest.}, author = {Henzinger, Monika H and Krinninger, Sebastian and Nanongkai, Danupon}, issn = {1557-735X}, journal = {Journal of the ACM}, number = {6}, pages = {1--40}, publisher = {Association for Computing Machinery}, title = {{Decremental single-source shortest paths on undirected graphs in near-linear total update time}}, doi = {10.1145/3218657}, volume = {65}, year = {2018}, } @inproceedings{11872, abstract = {We design fast dynamic algorithms for proper vertex and edge colorings in a graph undergoing edge insertions and deletions. In the static setting, there are simple linear time algorithms for (Δ + 1)- vertex coloring and (2Δ – 1)-edge coloring in a graph with maximum degree Δ. It is natural to ask if we can efficiently maintain such colorings in the dynamic setting as well. We get the following three results. (1) We present a randomized algorithm which maintains a (Δ + 1)-vertex coloring with O(log Δ) expected amortized update time. (2) We present a deterministic algorithm which maintains a (1 + o(1)Δ-vertex coloring with O(polylog Δ) amortized update time. (3) We present a simple, deterministic algorithm which maintains a (2Δ – 1)-edge coloring with O(log Δ) worst-case update time. This improves the recent O(Δ)-edge coloring algorithm with worst-case update time [4].}, author = {Bhattacharya, Sayan and Chakrabarty, Deeparnab and Henzinger, Monika H and Nanongkai, Danupon}, booktitle = {29th Annual ACM-SIAM Symposium on Discrete Algorithms}, location = {New Orleans, LA, United States}, pages = {1 -- 20}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Dynamic algorithms for graph coloring}}, doi = {10.1137/1.9781611975031.1}, year = {2018}, } @inproceedings{11882, abstract = {The minimum cut problem for an undirected edge-weighted graph asks us to divide its set of nodes into two blocks while minimizing the weight sum of the cut edges. Here, we introduce a linear-time algorithm to compute near-minimum cuts. Our algorithm is based on cluster contraction using label propagation and Padberg and Rinaldi's contraction heuristics [SIAM Review, 1991]. We give both sequential and shared-memory parallel implementations of our algorithm. Extensive experiments on both real-world and generated instances show that our algorithm finds the optimal cut on nearly all instances significantly faster than other state-of-the-art exact algorithms, and our error rate is lower than that of other heuristic algorithms. In addition, our parallel algorithm shows good scalability.}, author = {Henzinger, Monika H and Noe, Alexander and Schulz, Christian and Strash, Darren}, booktitle = {20th Workshop on Algorithm Engineering and Experiments}, location = {New Orleans, LA, United States}, pages = {48--61}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Practical minimum cut algorithms}}, doi = {10.1137/1.9781611975055.5}, year = {2018}, } @article{11890, abstract = {We present the first deterministic data structures for maintaining approximate minimum vertex cover and maximum matching in a fully dynamic graph 𝐺=(𝑉,𝐸), with |𝑉|=𝑛 and |𝐸|=𝑚, in 𝑜(𝑚‾‾√) time per update. In particular, for minimum vertex cover, we provide deterministic data structures for maintaining a (2+𝜖) approximation in 𝑂(log𝑛/𝜖2) amortized time per update. For maximum matching, we show how to maintain a (3+𝜖) approximation in 𝑂(min(𝑛√/𝜖,𝑚1/3/𝜖2) amortized time per update and a (4+𝜖) approximation in 𝑂(𝑚1/3/𝜖2) worst-case time per update. Our data structure for fully dynamic minimum vertex cover is essentially near-optimal and settles an open problem by Onak and Rubinfeld [in 42nd ACM Symposium on Theory of Computing, Cambridge, MA, ACM, 2010, pp. 457--464].}, author = {Bhattacharya, Sayan and Henzinger, Monika H and Italiano, Giuseppe F.}, issn = {1095-7111}, journal = {SIAM Journal on Computing}, number = {3}, pages = {859--887}, publisher = {Society for Industrial & Applied Mathematics}, title = {{Deterministic fully dynamic data structures for vertex cover and matching}}, doi = {10.1137/140998925}, volume = {47}, year = {2018}, } @inproceedings{11911, abstract = {It is common knowledge that there is no single best strategy for graph clustering, which justifies a plethora of existing approaches. In this paper, we present a general memetic algorithm, VieClus, to tackle the graph clustering problem. This algorithm can be adapted to optimize different objective functions. A key component of our contribution are natural recombine operators that employ ensemble clusterings as well as multi-level techniques. Lastly, we combine these techniques with a scalable communication protocol, producing a system that is able to compute high-quality solutions in a short amount of time. We instantiate our scheme with local search for modularity and show that our algorithm successfully improves or reproduces all entries of the 10th DIMACS implementation challenge under consideration using a small amount of time.}, author = {Biedermann, Sonja and Henzinger, Monika H and Schulz, Christian and Schuster, Bernhard}, booktitle = {17th International Symposium on Experimental Algorithms}, isbn = {9783959770705}, issn = {1868-8969}, location = {L'Aquila, Italy}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Memetic graph clustering}}, doi = {10.4230/LIPICS.SEA.2018.3}, volume = {103}, year = {2018}, } @article{11958, abstract = {Solid reagents, leaching catalysts, and heterogeneous photocatalysts are commonly employed in batch processes but are ill-suited for continuous-flow chemistry. Heterogeneous catalysts for thermal reactions are typically used in packed-bed reactors, which cannot be penetrated by light and thus are not suitable for photocatalytic reactions involving solids. We demonstrate that serial micro-batch reactors (SMBRs) allow for the continuous utilization of solid materials together with liquids and gases in flow. This technology was utilized to develop selective and efficient fluorination reactions using a modified graphitic carbon nitride heterogeneous catalyst instead of costly homogeneous metal polypyridyl complexes. The merger of this inexpensive, recyclable catalyst and the SMBR approach enables sustainable and scalable photocatalysis.}, author = {Pieber, Bartholomäus and Shalom, Menny and Antonietti, Markus and Seeberger, Peter H. and Gilmore, Kerry}, issn = { 1521-3773}, journal = {Angewandte Chemie International Edition}, number = {31}, pages = {9976--9979}, publisher = {Wiley}, title = {{Continuous heterogeneous photocatalysis in serial micro-batch reactors}}, doi = {10.1002/anie.201712568}, volume = {57}, year = {2018}, } @article{1215, abstract = {Two generalizations of Itô formula to infinite-dimensional spaces are given. The first one, in Hilbert spaces, extends the classical one by taking advantage of cancellations when they occur in examples and it is applied to the case of a group generator. The second one, based on the previous one and a limit procedure, is an Itô formula in a special class of Banach spaces having a product structure with the noise in a Hilbert component; again the key point is the extension due to a cancellation. This extension to Banach spaces and in particular the specific cancellation are motivated by path-dependent Itô calculus.}, author = {Flandoli, Franco and Russo, Francesco and Zanco, Giovanni A}, journal = {Journal of Theoretical Probability}, number = {2}, pages = {789--826}, publisher = {Springer}, title = {{Infinite-dimensional calculus under weak spatial regularity of the processes}}, doi = {10.1007/s10959-016-0724-2}, volume = {31}, year = {2018}, } @article{124, abstract = {By investigating the in situ chemical and O-isotope compositions of olivine in lightly sintered dust agglomerates from the early Solar System, we constrain their origins and the retention of dust in the protoplanetary disk. The grain sizes of silicates in these agglomeratic olivine (AO) chondrules indicate that the grain sizes of chondrule precursors in the Renazzo-like carbonaceous (CR) chondrites ranged from <1 to 80 µm. We infer this grain size range to be equivalent to the size range for dust in the early Solar System. AO chondrules may contain, but are not solely composed of, recycled fragments of earlier formed chondrules. They also contain 16O-rich olivine related to amoeboid olivine aggregates and represent the best record of chondrule-precursor materials. AO chondrules contain one or more large grains, sometimes similar to FeO-poor (type I) and/or FeO-rich (type II) chondrules, while others contain a type II chondrule core. These morphologies are consistent with particle agglomeration by electrostatic charging of grains during collision, a process that may explain solid agglomeration in the protoplanetary disk in the micrometer size regime. The petrographic, isotopic, and chemical compositions of AO chondrules are consistent with chondrule formation by large-scale shocks, bow shocks, and current sheets. The petrographic, isotopic, and chemical similarities between AO chondrules in CR chondrites and chondrule-like objects from comet 81P/Wild 2 indicate that comets contain AO chondrules. We infer that these AO chondrules likely formed in the inner Solar System and migrated to the comet forming region at least 3 Ma after the formation of the first Solar System solids. Observations made in this study imply that the protoplanetary disk retained a dusty disk at least ∼3.7 Ma after the formation of the first Solar System solids, longer than half of the dusty accretion disks observed around other stars.}, author = {Waitukaitis, Scott R and Schrader, Devin and Nagashima, Kazuhide and Davidson, Jemma and Mccoy, Timothy and Conolly Jr, Harold and Lauretta, Dante}, journal = {Geochimica et Cosmochimica Acta}, pages = {405 -- 421}, publisher = {Elsevier}, title = {{The retention of dust in protoplanetary disks: evidence from agglomeration olivine chondrules from the outer solar system}}, doi = {10.1016/j.gca.2017.12.014}, volume = {223}, year = {2018}, } @article{125, abstract = {Many fields of study, including medical imaging, granular physics, colloidal physics, and active matter, require the precise identification and tracking of particle-like objects in images. While many algorithms exist to track particles in diffuse conditions, these often perform poorly when particles are densely packed together—as in, for example, solid-like systems of granular materials. Incorrect particle identification can have significant effects on the calculation of physical quantities, which makes the development of more precise and faster tracking algorithms a worthwhile endeavor. In this work, we present a new tracking algorithm to identify particles in dense systems that is both highly accurate and fast. We demonstrate the efficacy of our approach by analyzing images of dense, solid-state granular media, where we achieve an identification error of 5% in the worst evaluated cases. Going further, we propose a parallelization strategy for our algorithm using a GPU, which results in a speedup of up to 10× when compared to a sequential CPU implementation in C and up to 40× when compared to the reference MATLAB library widely used for particle tracking. Our results extend the capabilities of state-of-the-art particle tracking methods by allowing fast, high-fidelity detection in dense media at high resolutions.}, author = {Cerda, Mauricio and Waitukaitis, Scott R and Navarro, Cristóbal and Silva, Juan and Mujica, Nicolás and Hitschfeld, Nancy}, journal = {Computer Physics Communications}, pages = {8 -- 16}, publisher = {Elsevier}, title = {{A high-speed tracking algorithm for dense granular media}}, doi = {10.1016/j.cpc.2018.02.010}, volume = {227}, year = {2018}, } @article{126, abstract = {The Leidenfrost effect occurs when a liquid or stiff sublimable solid near a hot surface creates enough vapor beneath it to lift itself up and float. In contrast, vaporizable soft solids, e.g., hydrogels, have been shown to exhibit persistent bouncing - the elastic Leidenfrost effect. By carefully lowering hydrogel spheres towards a hot surface, we discover that they are also capable of floating. The bounce-to-float transition is controlled by the approach velocity and temperature, analogously to the "dynamic Leidenfrost effect." For the floating regime, we measure power-law scalings for the gap geometry, which we explain with a model that couples the vaporization rate to the spherical shape. Our results reveal that hydrogels are a promising pathway for controlling floating Leidenfrost objects through shape.}, author = {Waitukaitis, Scott R and Harth, Kirsten and Van Hecke, Martin}, journal = {Physical Review Letters}, number = {4}, publisher = {American Physical Society}, title = {{From bouncing to floating: the Leidenfrost effect with hydrogel spheres}}, doi = {10.1103/PhysRevLett.121.048001}, volume = {121}, year = {2018}, } @article{127, abstract = {The ideas of topology are breaking ground in origami-based metamaterials. Experiments now show that certain shapes — doughnuts included — exhibit topological bistability, and can be made to click between different topologically stable states.}, author = {Waitukaitis, Scott R}, journal = {Nature Physics}, number = {8}, pages = {777 -- 778}, publisher = {Nature Publishing Group}, title = {{Clicks for doughnuts}}, doi = {10.1038/s41567-018-0160-6}, volume = {14}, year = {2018}, } @inproceedings{174, abstract = {We survey recent efforts to quantify failures of the Hasse principle in families of rationally connected varieties.}, author = {Browning, Timothy D}, location = {Salt Lake City, Utah, USA}, number = {2}, pages = {89 -- 102}, publisher = {American Mathematical Society}, title = {{How often does the Hasse principle hold?}}, doi = {10.1090/pspum/097.2/01700}, volume = {97}, year = {2018}, } @article{176, abstract = {For a general class of non-negative functions defined on integral ideals of number fields, upper bounds are established for their average over the values of certain principal ideals that are associated to irreducible binary forms with integer coefficients.}, author = {Browning, Timothy D and Sofos, Efthymios}, journal = {International Journal of Nuber Theory}, number = {3}, pages = {547--567}, publisher = {World Scientific Publishing}, title = {{Averages of arithmetic functions over principal ideals}}, doi = {10.1142/S1793042119500283}, volume = {15}, year = {2018}, } @article{178, abstract = {We give an upper bound for the number of rational points of height at most B, lying on a surface defined by a quadratic form Q. The bound shows an explicit dependence on Q. It is optimal with respect to B, and is also optimal for typical forms Q.}, author = {Browning, Timothy D and Heath-Brown, Roger}, issn = {2397-3129}, journal = {Discrete Analysis}, pages = {1 -- 29}, publisher = {Alliance of Diamond Open Access Journals}, title = {{Counting rational points on quadric surfaces}}, doi = {10.19086/da.4375}, volume = {15}, year = {2018}, } @inproceedings{185, abstract = {We resolve in the affirmative conjectures of A. Skopenkov and Repovš (1998), and M. Skopenkov (2003) generalizing the classical Hanani-Tutte theorem to the setting of approximating maps of graphs on 2-dimensional surfaces by embeddings. Our proof of this result is constructive and almost immediately implies an efficient algorithm for testing whether a given piecewise linear map of a graph in a surface is approximable by an embedding. More precisely, an instance of this problem consists of (i) a graph G whose vertices are partitioned into clusters and whose inter-cluster edges are partitioned into bundles, and (ii) a region R of a 2-dimensional compact surface M given as the union of a set of pairwise disjoint discs corresponding to the clusters and a set of pairwise disjoint "pipes" corresponding to the bundles, connecting certain pairs of these discs. We are to decide whether G can be embedded inside M so that the vertices in every cluster are drawn in the corresponding disc, the edges in every bundle pass only through its corresponding pipe, and every edge crosses the boundary of each disc at most once.}, author = {Fulek, Radoslav and Kynčl, Jan}, isbn = {978-3-95977-066-8}, location = {Budapest, Hungary}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Hanani-Tutte for approximating maps of graphs}}, doi = {10.4230/LIPIcs.SoCG.2018.39}, volume = {99}, year = {2018}, } @inproceedings{188, abstract = {Smallest enclosing spheres of finite point sets are central to methods in topological data analysis. Focusing on Bregman divergences to measure dissimilarity, we prove bounds on the location of the center of a smallest enclosing sphere. These bounds depend on the range of radii for which Bregman balls are convex.}, author = {Edelsbrunner, Herbert and Virk, Ziga and Wagner, Hubert}, location = {Budapest, Hungary}, pages = {35:1 -- 35:13}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Smallest enclosing spheres and Chernoff points in Bregman geometry}}, doi = {10.4230/LIPIcs.SoCG.2018.35}, volume = {99}, year = {2018}, } @article{2015, abstract = {We consider the problem of learning a Bayesian network or directed acyclic graph model from observational data. A number of constraint‐based, score‐based and hybrid algorithms have been developed for this purpose. Statistical consistency guarantees of these algorithms rely on the faithfulness assumption, which has been shown to be restrictive especially for graphs with cycles in the skeleton. We here propose the sparsest permutation (SP) algorithm, showing that learning Bayesian networks is possible under strictly weaker assumptions than faithfulness. This comes at a computational price, thereby indicating a statistical‐computational trade‐off for causal inference algorithms. In the Gaussian noiseless setting, we prove that the SP algorithm boils down to finding the permutation of the variables with the sparsest Cholesky decomposition of the inverse covariance matrix, which is equivalent to ℓ0‐penalized maximum likelihood estimation. We end with a simulation study showing that in line with the proven stronger consistency guarantees, and the SP algorithm compares favourably to standard causal inference algorithms in terms of accuracy for a given sample size.}, author = {Raskutti, Garvesh and Uhler, Caroline}, journal = {STAT}, number = {1}, publisher = {Wiley}, title = {{Learning directed acyclic graphs based on sparsest permutations}}, doi = {10.1002/sta4.183}, volume = {7}, year = {2018}, } @article{306, abstract = {A cornerstone of statistical inference, the maximum entropy framework is being increasingly applied to construct descriptive and predictive models of biological systems, especially complex biological networks, from large experimental data sets. Both its broad applicability and the success it obtained in different contexts hinge upon its conceptual simplicity and mathematical soundness. Here we try to concisely review the basic elements of the maximum entropy principle, starting from the notion of ‘entropy’, and describe its usefulness for the analysis of biological systems. As examples, we focus specifically on the problem of reconstructing gene interaction networks from expression data and on recent work attempting to expand our system-level understanding of bacterial metabolism. Finally, we highlight some extensions and potential limitations of the maximum entropy approach, and point to more recent developments that are likely to play a key role in the upcoming challenges of extracting structures and information from increasingly rich, high-throughput biological data.}, author = {De Martino, Andrea and De Martino, Daniele}, journal = {Heliyon}, number = {4}, publisher = {Elsevier}, title = {{An introduction to the maximum entropy approach and its application to inference problems in biology}}, doi = {10.1016/j.heliyon.2018.e00596}, volume = {4}, year = {2018}, } @book{3300, abstract = {This book first explores the origins of this idea, grounded in theoretical work on temporal logic and automata. The editors and authors are among the world's leading researchers in this domain, and they contributed 32 chapters representing a thorough view of the development and application of the technique. Topics covered include binary decision diagrams, symbolic model checking, satisfiability modulo theories, partial-order reduction, abstraction, interpolation, concurrency, security protocols, games, probabilistic model checking, and process algebra, and chapters on the transfer of theory to industrial practice, property specification languages for hardware, and verification of real-time systems and hybrid systems. The book will be valuable for researchers and graduate students engaged with the development of formal methods and verification tools.}, author = {Clarke, Edmund M. and Henzinger, Thomas A and Veith, Helmut and Bloem, Roderick}, isbn = {978-3-319-10574-1}, pages = {XLVIII, 1212}, publisher = {Springer Nature}, title = {{Handbook of Model Checking}}, doi = {10.1007/978-3-319-10575-8}, year = {2018}, } @inbook{37, abstract = {Developmental processes are inherently dynamic and understanding them requires quantitative measurements of gene and protein expression levels in space and time. While live imaging is a powerful approach for obtaining such data, it is still a challenge to apply it over long periods of time to large tissues, such as the embryonic spinal cord in mouse and chick. Nevertheless, dynamics of gene expression and signaling activity patterns in this organ can be studied by collecting tissue sections at different developmental stages. In combination with immunohistochemistry, this allows for measuring the levels of multiple developmental regulators in a quantitative manner with high spatiotemporal resolution. The mean protein expression levels over time, as well as embryo-to-embryo variability can be analyzed. A key aspect of the approach is the ability to compare protein levels across different samples. This requires a number of considerations in sample preparation, imaging and data analysis. Here we present a protocol for obtaining time course data of dorsoventral expression patterns from mouse and chick neural tube in the first 3 days of neural tube development. The described workflow starts from embryo dissection and ends with a processed dataset. Software scripts for data analysis are included. The protocol is adaptable and instructions that allow the user to modify different steps are provided. Thus, the procedure can be altered for analysis of time-lapse images and applied to systems other than the neural tube.}, author = {Zagórski, Marcin P and Kicheva, Anna}, booktitle = {Morphogen Gradients }, isbn = {978-1-4939-8771-9}, issn = {1064-3745}, pages = {47 -- 63}, publisher = {Springer Nature}, title = {{Measuring dorsoventral pattern and morphogen signaling profiles in the growing neural tube}}, doi = {10.1007/978-1-4939-8772-6_4}, volume = {1863}, year = {2018}, } @article{305, abstract = {The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks.}, author = {Misun, Patrick and Birchler, Axel and Lang, Moritz and Hierlemann, Andreas and Frey, Olivier}, journal = {Methods in Molecular Biology}, pages = {183 -- 202}, publisher = {Springer}, title = {{Fabrication and operation of microfluidic hanging drop networks}}, doi = {10.1007/978-1-4939-7792-5_15}, volume = {1771}, year = {2018}, } @inproceedings{325, abstract = {Probabilistic programs extend classical imperative programs with real-valued random variables and random branching. The most basic liveness property for such programs is the termination property. The qualitative (aka almost-sure) termination problem asks whether a given program program terminates with probability 1. While ranking functions provide a sound and complete method for non-probabilistic programs, the extension of them to probabilistic programs is achieved via ranking supermartingales (RSMs). Although deep theoretical results have been established about RSMs, their application to probabilistic programs with nondeterminism has been limited only to programs of restricted control-flow structure. For non-probabilistic programs, lexicographic ranking functions provide a compositional and practical approach for termination analysis of real-world programs. In this work we introduce lexicographic RSMs and show that they present a sound method for almost-sure termination of probabilistic programs with nondeterminism. We show that lexicographic RSMs provide a tool for compositional reasoning about almost-sure termination, and for probabilistic programs with linear arithmetic they can be synthesized efficiently (in polynomial time). We also show that with additional restrictions even asymptotic bounds on expected termination time can be obtained through lexicographic RSMs. Finally, we present experimental results on benchmarks adapted from previous work to demonstrate the effectiveness of our approach.}, author = {Agrawal, Sheshansh and Chatterjee, Krishnendu and Novotny, Petr}, location = {Los Angeles, CA, USA}, number = {POPL}, publisher = {ACM}, title = {{Lexicographic ranking supermartingales: an efficient approach to termination of probabilistic programs}}, doi = {10.1145/3158122}, volume = {2}, year = {2018}, } @article{394, abstract = {The valley pseudospin in monolayer transition metal dichalcogenides (TMDs) has been proposed as a new way to manipulate information in various optoelectronic devices. This relies on a large valley polarization that remains stable over long time scales (hundreds of nanoseconds). However, time-resolved measurements report valley lifetimes of only a few picoseconds. This has been attributed to mechanisms such as phonon-mediated intervalley scattering and a precession of the valley pseudospin through electron-hole exchange. Here we use transient spin grating to directly measure the valley depolarization lifetime in monolayer MoSe2. We find a fast valley decay rate that scales linearly with the excitation density at different temperatures. This establishes the presence of strong exciton-exciton Coulomb exchange interactions enhancing the valley depolarization. Our work highlights the microscopic processes inhibiting the efficient use of the exciton valley pseudospin in monolayer TMDs. }, author = {Mahmood, Fahad and Alpichshev, Zhanybek and Lee, Yi and Kong, Jing and Gedik, Nuh}, journal = {Nano Letters}, number = {1}, pages = {223 -- 228}, publisher = {American Chemical Society}, title = {{Observation of exciton-exciton interaction mediated valley Depolarization in Monolayer MoSe2}}, doi = {10.1021/acs.nanolett.7b03953}, volume = {18}, year = {2018}, } @inbook{408, abstract = {Adventitious roots (AR) are de novo formed roots that emerge from any part of the plant or from callus in tissue culture, except root tissue. The plant tissue origin and the method by which they are induced determine the physiological properties of emerged ARs. Hence, a standard method encompassing all types of AR does not exist. Here we describe a method for the induction and analysis of AR that emerge from the etiolated hypocotyl of dicot plants. The hypocotyl is formed during embryogenesis and shows a determined developmental pattern which usually does not involve AR formation. However, the hypocotyl shows propensity to form de novo roots under specific circumstances such as removal of the root system, high humidity or flooding, or during de-etiolation. The hypocotyl AR emerge from a pericycle-like cell layer surrounding the vascular tissue of the central cylinder, which is reminiscent to the developmental program of lateral roots. Here we propose an easy protocol for in vitro hypocotyl AR induction from etiolated Arabidopsis seedlings.}, author = {Trinh, Hoang and Verstraeten, Inge and Geelen, Danny}, booktitle = {Root Development }, issn = {1064-3745}, pages = {95 -- 102}, publisher = {Springer Nature}, title = {{In vitro assay for induction of adventitious rooting on intact arabidopsis hypocotyls}}, doi = {10.1007/978-1-4939-7747-5_7}, volume = {1761}, year = {2018}, }