TY - JOUR
AB - We study the BCS energy gap Ξ in the high–density limit and derive an asymptotic formula, which strongly depends on the strength of the interaction potential V on the Fermi surface. In combination with the recent result by one of us (Math. Phys. Anal. Geom. 25, 3, 2022) on the critical temperature Tc at high densities, we prove the universality of the ratio of the energy gap and the critical temperature.
AU - Henheik, Sven Joscha
AU - Lauritsen, Asbjørn Bækgaard
ID - 11732
JF - Journal of Statistical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0022-4715
TI - The BCS energy gap at high density
VL - 189
ER -
TY - JOUR
AB - We consider the flow of two viscous and incompressible fluids within a bounded domain modeled by means of a two-phase Navier–Stokes system. The two fluids are assumed to be immiscible, meaning that they are separated by an interface. With respect to the motion of the interface, we consider pure transport by the fluid flow. Along the boundary of the domain, a complete slip boundary condition for the fluid velocities and a constant ninety degree contact angle condition for the interface are assumed. In the present work, we devise for the resulting evolution problem a suitable weak solution concept based on the framework of varifolds and establish as the main result a weak-strong uniqueness principle in 2D. The proof is based on a relative entropy argument and requires a non-trivial further development of ideas from the recent work of Fischer and the first author (Arch. Ration. Mech. Anal. 236, 2020) to incorporate the contact angle condition. To focus on the effects of the necessarily singular geometry of the evolving fluid domains, we work for simplicity in the regime of same viscosities for the two fluids.
AU - Hensel, Sebastian
AU - Marveggio, Alice
ID - 11842
IS - 3
JF - Journal of Mathematical Fluid Mechanics
SN - 1422-6928
TI - Weak-strong uniqueness for the Navier–Stokes equation for two fluids with ninety degree contact angle and same viscosities
VL - 24
ER -
TY - JOUR
AB - Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer’s and Parkinson’s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process.
AU - Toprakcioglu, Zenon
AU - Kamada, Ayaka
AU - Michaels, Thomas C.T.
AU - Xie, Mengqi
AU - Krausser, Johannes
AU - Wei, Jiapeng
AU - Šarić, Anđela
AU - Vendruscolo, Michele
AU - Knowles, Tuomas P.J.
ID - 11841
IS - 31
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
TI - Adsorption free energy predicts amyloid protein nucleation rates
VL - 119
ER -
TY - CONF
AB - The medial axis of a set consists of the points in the ambient space without a unique closest point on the original set. Since its introduction, the medial axis has been used extensively in many applications as a method of computing a topologically equivalent skeleton. Unfortunately, one limiting factor in the use of the medial axis of a smooth manifold is that it is not necessarily topologically stable under small perturbations of the manifold. To counter these instabilities various prunings of the medial axis have been proposed. Here, we examine one type of pruning, called burning. Because of the good experimental results, it was hoped that the burning method of simplifying the medial axis would be stable. In this work we show a simple example that dashes such hopes based on Bing’s house with two rooms, demonstrating an isotopy of a shape where the medial axis goes from collapsible to non-collapsible.
AU - Chambers, Erin
AU - Fillmore, Christopher D
AU - Stephenson, Elizabeth R
AU - Wintraecken, Mathijs
ED - Goaoc, Xavier
ED - Kerber, Michael
ID - 11428
SN - 1868-8969
T2 - 38th International Symposium on Computational Geometry
TI - A cautionary tale: Burning the medial axis is unstable
VL - 224
ER -
TY - JOUR
AB - A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.
AU - Tomasek, Kathrin
AU - Leithner, Alexander F
AU - Glatzová, Ivana
AU - Lukesch, Michael S.
AU - Guet, Calin C
AU - Sixt, Michael K
ID - 11843
JF - eLife
TI - Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
VL - 11
ER -
TY - JOUR
AB - This paper is a continuation of Part I of this project, where we developed a new local well-posedness theory for nonlinear stochastic PDEs with Gaussian noise. In the current Part II we consider blow-up criteria and regularization phenomena. As in Part I we can allow nonlinearities with polynomial growth and rough initial values from critical spaces. In the first main result we obtain several new blow-up criteria for quasi- and semilinear stochastic evolution equations. In particular, for semilinear equations we obtain a Serrin type blow-up criterium, which extends a recent result of Prüss–Simonett–Wilke (J Differ Equ 264(3):2028–2074, 2018) to the stochastic setting. Blow-up criteria can be used to prove global well-posedness for SPDEs. As in Part I, maximal regularity techniques and weights in time play a central role in the proofs. Our second contribution is a new method to bootstrap Sobolev and Hölder regularity in time and space, which does not require smoothness of the initial data. The blow-up criteria are at the basis of these new methods. Moreover, in applications the bootstrap results can be combined with our blow-up criteria, to obtain efficient ways to prove global existence. This gives new results even in classical 𝐿2-settings, which we illustrate for a concrete SPDE. In future works in preparation we apply the results of the current paper to obtain global well-posedness results and regularity for several concrete SPDEs. These include stochastic Navier–Stokes equations, reaction– diffusion equations and the Allen–Cahn equation. Our setting allows to put these SPDEs into a more flexible framework, where less restrictions on the nonlinearities are needed, and we are able to treat rough initial values from critical spaces. Moreover, we will obtain higher-order regularity results.
AU - Agresti, Antonio
AU - Veraar, Mark
ID - 11858
IS - 2
JF - Journal of Evolution Equations
KW - Mathematics (miscellaneous)
SN - 1424-3199
TI - Nonlinear parabolic stochastic evolution equations in critical spaces part II
VL - 22
ER -
TY - CHAP
AB - Streaky structures in the boundary layers are often generated by surface roughness elements and/or free-stream turbulence, and are known to have significant effects on boundary-layer instability. In this paper, we investigate the impact of two forms of streaks on the instability of supersonic boundary layers. The first concerns the streaks generated by an array of spanwise periodic and streamwise elongated surface roughness elements, and our interest is how these streaks influence the lower-branch viscous first modes, whose characteristic wavelength and frequency are on the classical triple-deck scales. By adapting the triple-deck theory in the incompressible regime to the supersonic one, we first derived a simplified system which allows for efficient calculation of the streaks. The asymptotic analysis simplifies a bi-global eigenvalue problem to a one-dimensional problem in the spanwise direction, showing that the instability is controlled at leading order solely by the spanwise-dependent wall shear. In the fundamental configuration, the streaks stabilize first modes at low frequencies but destabilize the high-frequency ones. In the subharmonic configuration, the streaks generally destabilize the first mode across the entire frequency band. Importantly, the spanwise even modes are of radiating nature, i.e. they emit acoustic waves spontaneously to the far field. Streaks of the second form are generated by low-frequency vortical disturbances representing free-stream turbulence. They alter the flow in the entire layer and their effects on instability are investigated by solving the inviscid bi-global eigenvalue problem. Different from the incompressible case, a multitude of compressible instability modes exists, of which the dominant mode is an inviscid instability associated with the spanwise shear. In addition, there exists a separate branch of instability modes that have smaller growth rates but are spontaneously radiating.
AU - Liu, Jianxin
AU - Marensi, Elena
AU - Wu, Xuesong
ED - Sherwin, Spencer
ED - Schmid, Peter
ED - Wu, Xuesong
ID - 10820
SN - 1875-3507
T2 - IUTAM Laminar-Turbulent Transition
TI - Effects of streaky structures on the instability of supersonic boundary layers
VL - 38
ER -
TY - CONF
AB - In the stochastic population protocol model, we are given a connected graph with n nodes, and in every time step, a scheduler samples an edge of the graph uniformly at random and the nodes connected by this edge interact. A fundamental task in this model is stable leader election, in which all nodes start in an identical state and the aim is to reach a configuration in which (1) exactly one node is elected as leader and (2) this node remains as the unique leader no matter what sequence of interactions follows. On cliques, the complexity of this problem has recently been settled: time-optimal protocols stabilize in Θ(n log n) expected steps using Θ(log log n) states, whereas protocols that use O(1) states require Θ(n2) expected steps.
In this work, we investigate the complexity of stable leader election on general graphs. We provide the first non-trivial time lower bounds for leader election on general graphs, showing that, when moving beyond cliques, the complexity landscape of leader election becomes very diverse: the time required to elect a leader can range from O(1) to Θ(n3) expected steps. On the upper bound side, we first observe that there exists a protocol that is time-optimal on many graph families, but uses polynomially-many states. In contrast, we give a near-time-optimal protocol that uses only O(log2n) states that is at most a factor log n slower. Finally, we show that the constant-state protocol of Beauquier et al. [OPODIS 2013] is at most a factor n log n slower than the fast polynomial-state protocol. Moreover, among constant-state protocols, this protocol has near-optimal average case complexity on dense random graphs.
AU - Alistarh, Dan-Adrian
AU - Rybicki, Joel
AU - Voitovych, Sasha
ID - 11844
SN - 9781450392624
T2 - Proceedings of the Annual ACM Symposium on Principles of Distributed Computing
TI - Near-optimal leader election in population protocols on graphs
ER -
TY - JOUR
AB - We study the many-body dynamics of an initially factorized bosonic wave function in the mean-field regime. We prove large deviation estimates for the fluctuations around the condensate. We derive an upper bound extending a recent result to more general interactions. Furthermore, we derive a new lower bound which agrees with the upper bound in leading order.
AU - Rademacher, Simone Anna Elvira
AU - Seiringer, Robert
ID - 11917
JF - Journal of Statistical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0022-4715
TI - Large deviation estimates for weakly interacting bosons
VL - 188
ER -
TY - JOUR
AB - The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.
AU - Belyaeva, Vera
AU - Wachner, Stephanie
AU - György, Attila
AU - Emtenani, Shamsi
AU - Gridchyn, Igor
AU - Akhmanova, Maria
AU - Linder, M
AU - Roblek, Marko
AU - Sibilia, M
AU - Siekhaus, Daria E
ID - 10614
IS - 1
JF - PLoS Biology
SN - 1544-9173
TI - Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila
VL - 20
ER -
TY - THES
AB - The infiltration of immune cells into tissues underlies the establishment of tissue-resident
macrophages and responses to infections and tumors. However, the mechanisms immune
cells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.
In this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to
overcome the tissue barrier of the germband in the embryo. One strategy is the strengthening
of the actin cortex through developmentally controlled transcriptional regulation induced by
the Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces
expression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the
activated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical
strength allows hemocytes to overcome the physical resistance of the surrounding tissue and
translocate their nucleus to move forward. This mechanism affects the speed of migration
when hemocytes face a confined environment in vivo.
Another aspect of the invasion process is the initial step of the leading hemocytes entering
the tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel
subpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads
penetration into the germband. Hemocytes that are deficient in BMP signaling activation
show impaired persistence at the tissue entry, while their migration speed remains
unaffected.
This suggests that there might be different mechanisms controlling immune cell migration
within the confined environment in vivo, one of these being the general ability to overcome
the resistance of the surrounding tissue and another affecting the order of hemocytes that
collectively invade the tissue in a stream of individual cells.
Together, my findings provide deeper insights into transcriptional changes in immune
cells that enable efficient tissue invasion and pave the way for future studies investigating the
early colonization of tissues by macrophages in higher organisms. Moreover, they extend the
current view of Drosophila immune cell heterogeneity and point toward a potentially
conserved role for canonical BMP signaling in specifying immune cells that lead the migration
of tissue resident macrophages during embryogenesis.
AU - Wachner, Stephanie
ID - 11193
SN - 2663-337X
TI - Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells
ER -
TY - JOUR
AB - Squall lines are known to be the consequence of the interaction of low-level shear with cold pools associated with convective downdrafts. Also, as the magnitude of the shear increases beyond a critical shear, squall lines tend to orient themselves. The existing literature suggests that this orientation reduces incoming wind shear to the squall line, and maintains equilibrium between wind shear and cold pool spreading. Although this theory is widely accepted, very few quantitative studies have been conducted on supercritical regime especially. Here, we test this hypothesis with tropical squall lines obtained by imposing a vertical wind shear in cloud resolving simulations in radiative convective equilibrium. In the sub-critical regime, squall lines are perpendicular to the shear. In the super-critical regime, their orientation maintain the equilibrium, supporting existing theories. We also find that as shear increases, cold pools become more intense. However, this intensification has little impact on squall line orientation.
AU - Abramian, Sophie
AU - Muller, Caroline J
AU - Risi, Camille
ID - 10653
IS - 1
JF - Geophysical Research Letters
SN - 0094-8276
TI - Shear-convection interactions and orientation of tropical squall lines
VL - 49
ER -
TY - THES
AB - In this dissertation we study coboundary expansion of simplicial complex with a view of giving geometric applications.
Our main novel tool is an equivariant version of Gromov's celebrated Topological Overlap Theorem. The equivariant topological overlap theorem leads to various geometric applications including a quantitative non-embeddability result for sufficiently thick buildings (which partially resolves a conjecture of Tancer and Vorwerk) and an improved lower bound on the pair-crossing number of (bounded degree) expander graphs. Additionally, we will give new proofs for several known lower bounds for geometric problems such as the number of Tverberg partitions or the crossing number of complete bipartite graphs.
For the aforementioned applications one is naturally lead to study expansion properties of joins of simplicial complexes. In the presence of a special certificate for expansion (as it is the case, e.g., for spherical buildings), the join of two expanders is an expander. On the flip-side, we report quite some evidence that coboundary expansion exhibits very non-product-like behaviour under taking joins. For instance, we exhibit infinite families of graphs $(G_n)_{n\in \mathbb{N}}$ and $(H_n)_{n\in\mathbb{N}}$ whose join $G_n*H_n$ has expansion of lower order than the product of the expansion constant of the graphs. Moreover, we show an upper bound of $(d+1)/2^d$ on the normalized coboundary expansion constants for the complete multipartite complex $[n]^{*(d+1)}$ (under a mild divisibility condition on $n$).
Via the probabilistic method the latter result extends to an upper bound of $(d+1)/2^d+\varepsilon$ on the coboundary expansion constant of the spherical building associated with $\mathrm{PGL}_{d+2}(\mathbb{F}_q)$ for any $\varepsilon>0$ and sufficiently large $q=q(\varepsilon)$. This disproves a conjecture of Lubotzky, Meshulam and Mozes -- in a rather strong sense.
By improving on existing lower bounds we make further progress towards closing the gap between the known lower and upper bounds on the coboundary expansion constants of $[n]^{*(d+1)}$. The best improvements we achieve using computer-aided proofs and flag algebras. The exact value even for the complete $3$-partite $2$-dimensional complex $[n]^{*3}$ remains unknown but we are happy to conjecture a precise value for every $n$. %Moreover, we show that a previously shown lower bound on the expansion constant of the spherical building associated with $\mathrm{PGL}_{2}(\mathbb{F}_q)$ is not tight.
In a loosely structured, last chapter of this thesis we collect further smaller observations related to expansion. We point out a link between discrete Morse theory and a technique for showing coboundary expansion, elaborate a bit on the hardness of computing coboundary expansion constants, propose a new criterion for coboundary expansion (in a very dense setting) and give one way of making the folklore result that expansion of links is a necessary condition for a simplicial complex to be an expander precise.
AU - Wild, Pascal
ID - 11777
SN - 2663-337X
TI - High-dimensional expansion and crossing numbers of simplicial complexes
ER -
TY - JOUR
AB - A matching is compatible to two or more labeled point sets of size n with labels {1, . . . , n} if its straight-line drawing on each of these point sets is crossing-free. We study the maximum number of edges in a matching compatible to two or more labeled point sets in general position in the plane. We show that for any two labeled sets of n points in convex position there exists a compatible matching with ⌊√2n + 1 − 1⌋ edges. More generally, for any ℓ labeled point sets we construct compatible matchings of size Ω(n1/ℓ). As a corresponding upper bound, we use probabilistic arguments to show that for any ℓ given sets of n points there exists a labeling of each set such that the largest compatible matching has O(n2/(ℓ+1)) edges. Finally, we show that Θ(log n) copies of any set of n points are necessary and sufficient for the existence of labelings of these point sets such that any compatible matching consists only of a single edge.
AU - Aichholzer, Oswin
AU - Arroyo Guevara, Alan M
AU - Masárová, Zuzana
AU - Parada, Irene
AU - Perz, Daniel
AU - Pilz, Alexander
AU - Tkadlec, Josef
AU - Vogtenhuber, Birgit
ID - 11938
IS - 2
JF - Journal of Graph Algorithms and Applications
SN - 1526-1719
TI - On compatible matchings
VL - 26
ER -
TY - JOUR
AB - Most experimentally known high-pressure ice phases have a body-centred cubic (bcc) oxygen lattice. Our large-scale molecular-dynamics simulations with a machine-learning potential indicate that, amongst these bcc ice phases, ices VII, VII′ and X are the same thermodynamic phase under different conditions, whereas superionic ice VII″ has a first-order phase boundary with ice VII′. Moreover, at about 300 GPa, the transformation between ice X and the Pbcm phase has a sharp structural change but no apparent activation barrier, whilst at higher pressures the barrier gradually increases. Our study thus clarifies the phase behaviour of the high-pressure ices and reveals peculiar solid–solid transition mechanisms not known in other systems.
AU - Reinhardt, Aleks
AU - Bethkenhagen, Mandy
AU - Coppari, Federica
AU - Millot, Marius
AU - Hamel, Sebastien
AU - Cheng, Bingqing
ID - 11937
JF - Nature Communications
TI - Thermodynamics of high-pressure ice phases explored with atomistic simulations
VL - 13
ER -
TY - THES
AB - The ability to form and retrieve memories is central to survival. In mammals, the hippocampus
is a brain region essential to the acquisition and consolidation of new memories. It is also
involved in keeping track of one’s position in space and aids navigation. Although this
space-memory has been a source of contradiction, evidence supports the view that the role of
the hippocampus in navigation is memory, thanks to the formation of cognitive maps. First
introduced by Tolman in 1948, cognitive maps are generally used to organize experiences in
memory; however, the detailed mechanisms by which these maps are formed and stored are not
yet agreed upon. Some influential theories describe this process as involving three fundamental
steps: initial encoding by the hippocampus, interactions between the hippocampus and other
cortical areas, and long-term extra-hippocampal consolidation. In this thesis, I will show how
the investigation of cognitive maps of space helped to shed light on each of these three memory
processes.
The first study included in this thesis deals with the initial encoding of spatial memories in
the hippocampus. Much is known about encoding at the level of single cells, but less about
their co-activity or joint contribution to the encoding of novel spatial information. I will
describe the structure of an interaction network that allows for efficient encoding of noisy
spatial information during the first exploration of a novel environment.
The second study describes the interactions between the hippocampus and the prefrontal
cortex (PFC), two areas directly and indirectly connected. It is known that the PFC, in concert
with the hippocampus, is involved in various processes, including memory storage and spatial
navigation. Nonetheless, the detailed mechanisms by which PFC receives information from the
hippocampus are not clear. I will show how a transient improvement in theta phase locking of
PFC cells enables interactions of cell pairs across the two regions.
The third study describes the learning of behaviorally-relevant spatial locations in the hippocampus and the medial entorhinal cortex. I will show how the accumulation of firing around
goal locations, a correlate of learning, can shed light on the transition from short- to long-term
spatial memories and the speed of consolidation in different brain areas.
The studies included in this thesis represent the main scientific contributions of my Ph.D. They
involve statistical analyses and models of neural responses of cells in different brain areas of
rats executing spatial tasks. I will conclude the thesis by discussing the impact of the findings
on principles of memory formation and retention, including the mechanisms, the speed, and
the duration of these processes.
AU - Nardin, Michele
ID - 11932
SN - 2663-337X
TI - On the encoding, transfer, and consolidation of spatial memories
ER -
TY - GEN
AB - We determine an asymptotic formula for the number of integral points of
bounded height on a certain toric variety, which is incompatible with part of a
preprint by Chambert-Loir and Tschinkel. We provide an alternative
interpretation of the asymptotic formula we get. To do so, we construct an
analogue of Peyre's constant $\alpha$ and describe its relation to a new
obstruction to the Zariski density of integral points in certain regions of
varieties.
AU - Wilsch, Florian Alexander
ID - 10788
KW - Integral point
KW - toric variety
KW - Manin's conjecture
T2 - arXiv
TI - Integral points of bounded height on a certain toric variety
ER -
TY - THES
AB - Deep learning has enabled breakthroughs in challenging computing problems and has emerged as the standard problem-solving tool for computer vision and natural language processing tasks.
One exception to this trend is safety-critical tasks where robustness and resilience requirements contradict the black-box nature of neural networks.
To deploy deep learning methods for these tasks, it is vital to provide guarantees on neural network agents' safety and robustness criteria.
This can be achieved by developing formal verification methods to verify the safety and robustness properties of neural networks.
Our goal is to design, develop and assess safety verification methods for neural networks to improve their reliability and trustworthiness in real-world applications.
This thesis establishes techniques for the verification of compressed and adversarially trained models as well as the design of novel neural networks for verifiably safe decision-making.
First, we establish the problem of verifying quantized neural networks. Quantization is a technique that trades numerical precision for the computational efficiency of running a neural network and is widely adopted in industry.
We show that neglecting the reduced precision when verifying a neural network can lead to wrong conclusions about the robustness and safety of the network, highlighting that novel techniques for quantized network verification are necessary. We introduce several bit-exact verification methods explicitly designed for quantized neural networks and experimentally confirm on realistic networks that the network's robustness and other formal properties are affected by the quantization.
Furthermore, we perform a case study providing evidence that adversarial training, a standard technique for making neural networks more robust, has detrimental effects on the network's performance. This robustness-accuracy tradeoff has been studied before regarding the accuracy obtained on classification datasets where each data point is independent of all other data points. On the other hand, we investigate the tradeoff empirically in robot learning settings where a both, a high accuracy and a high robustness, are desirable.
Our results suggest that the negative side-effects of adversarial training outweigh its robustness benefits in practice.
Finally, we consider the problem of verifying safety when running a Bayesian neural network policy in a feedback loop with systems over the infinite time horizon. Bayesian neural networks are probabilistic models for learning uncertainties in the data and are therefore often used on robotic and healthcare applications where data is inherently stochastic.
We introduce a method for recalibrating Bayesian neural networks so that they yield probability distributions over safe decisions only.
Our method learns a safety certificate that guarantees safety over the infinite time horizon to determine which decisions are safe in every possible state of the system.
We demonstrate the effectiveness of our approach on a series of reinforcement learning benchmarks.
AU - Lechner, Mathias
ID - 11362
KW - neural networks
KW - verification
KW - machine learning
SN - 978-3-99078-017-6
TI - Learning verifiable representations
ER -
TY - CONF
AB - We present a formal framework for the online black-box monitoring of software using monitors with quantitative verdict functions. Quantitative verdict functions have several advantages. First, quantitative monitors can be approximate, i.e., the value of the verdict function does not need to correspond exactly to the value of the property under observation. Second, quantitative monitors can be quantified universally, i.e., for every possible observed behavior, the monitor tries to make the best effort to estimate the value of the property under observation. Third, quantitative monitors can watch boolean as well as quantitative properties, such as average response time. Fourth, quantitative monitors can use non-finite-state resources, such as counters. As a consequence, quantitative monitors can be compared according to how many resources they use (e.g., the number of counters) and how precisely they approximate the property under observation. This allows for a rich spectrum of cost-precision trade-offs in monitoring software.
AU - Henzinger, Thomas A
ID - 10891
SN - 0302-9743
T2 - Software Verification
TI - Quantitative monitoring of software
VL - 13124
ER -
TY - GEN
AB - Adversarial training (i.e., training on adversarially perturbed input data) is a well-studied method for making neural networks robust to potential adversarial attacks during inference. However, the improved robustness does not
come for free but rather is accompanied by a decrease in overall model accuracy and performance. Recent work has shown that, in practical robot learning applications, the effects of adversarial training do not pose a fair trade-off
but inflict a net loss when measured in holistic robot performance. This work revisits the robustness-accuracy trade-off in robot learning by systematically analyzing if recent advances in robust training methods and theory in
conjunction with adversarial robot learning can make adversarial training suitable for real-world robot applications. We evaluate a wide variety of robot learning tasks ranging from autonomous driving in a high-fidelity environment
amenable to sim-to-real deployment, to mobile robot gesture recognition. Our results demonstrate that, while these techniques make incremental improvements on the trade-off on a relative scale, the negative side-effects caused by
adversarial training still outweigh the improvements by an order of magnitude. We conclude that more substantial advances in robust learning methods are necessary before they can benefit robot learning tasks in practice.
AU - Lechner, Mathias
AU - Amini, Alexander
AU - Rus, Daniela
AU - Henzinger, Thomas A
ID - 11366
T2 - arXiv
TI - Revisiting the adversarial robustness-accuracy tradeoff in robot learning
ER -
TY - CONF
AB - Contract-based design is a promising methodology for taming the complexity of developing sophisticated systems. A formal contract distinguishes between assumptions, which are constraints that the designer of a component puts on the environments in which the component can be used safely, and guarantees, which are promises that the designer asks from the team that implements the component. A theory of formal contracts can be formalized as an interface theory, which supports the composition and refinement of both assumptions and guarantees.
Although there is a rich landscape of contract-based design methods that address functional and extra-functional properties, we present the first interface theory that is designed for ensuring system-wide security properties. Our framework provides a refinement relation and a composition operation that support both incremental design and independent implementability. We develop our theory for both stateless and stateful interfaces. We illustrate the applicability of our framework with an example inspired from the automotive domain.
AU - Bartocci, Ezio
AU - Ferrere, Thomas
AU - Henzinger, Thomas A
AU - Nickovic, Dejan
AU - Da Costa, Ana Oliveira
ID - 11355
SN - 0302-9743
T2 - Fundamental Approaches to Software Engineering
TI - Information-flow interfaces
VL - 13241
ER -
TY - JOUR
AB - The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.
AU - Ben Simon, Yoav
AU - Käfer, Karola
AU - Velicky, Philipp
AU - Csicsvari, Jozsef L
AU - Danzl, Johann G
AU - Jonas, Peter M
ID - 11951
JF - Nature Communications
KW - General Physics and Astronomy
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Chemistry
KW - Multidisciplinary
SN - 2041-1723
TI - A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory
VL - 13
ER -
TY - JOUR
AB - Maternally inherited Wolbachia transinfections are being introduced into natural mosquito populations to reduce the transmission of dengue, Zika, and other arboviruses. Wolbachia-induced cytoplasmic incompatibility provides a frequency-dependent reproductive advantage to infected females that can spread transinfections within and among populations. However, because transinfections generally reduce host fitness, they tend to spread within populations only after their frequency exceeds a critical threshold. This produces bistability with stable equilibrium frequencies at both 0 and 1, analogous to the bistability produced by underdominance between alleles or karyotypes and by population dynamics under Allee effects. Here, we analyze how stochastic frequency variation produced by finite population size can facilitate the local spread of variants with bistable dynamics into areas where invasion is unexpected from deterministic models. Our exemplar is the establishment of wMel Wolbachia in the Aedes aegypti population of Pyramid Estates (PE), a small community in far north Queensland, Australia. In 2011, wMel was stably introduced into Gordonvale, separated from PE by barriers to A. aegypti dispersal. After nearly 6 years during which wMel was observed only at low frequencies in PE, corresponding to an apparent equilibrium between immigration and selection, wMel rose to fixation by 2018. Using analytic approximations and statistical analyses, we demonstrate that the observed fixation of wMel at PE is consistent with both stochastic transition past an unstable threshold frequency and deterministic transformation produced by steady immigration at a rate just above the threshold required for deterministic invasion. The indeterminacy results from a delicate balance of parameters needed to produce the delayed transition observed. Our analyses suggest that once Wolbachia transinfections are established locally through systematic introductions, stochastic “threshold crossing” is likely to only minimally enhance spatial spread, providing a local ratchet that slightly—but systematically—aids area-wide transformation of disease-vector populations in heterogeneous landscapes.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 10604
IS - 1
JF - Evolution Letters
KW - genetics
KW - ecology
KW - evolution
KW - behavior and systematics
TI - Why did the Wolbachia transinfection cross the road? Drift, deterministic dynamics, and disease control
VL - 6
ER -
TY - JOUR
AB - The precursor conversion chemistry and surface chemistry of Cu3N and Cu3PdN nanocrystals are unknown or contested. Here, we first obtain phase-pure, colloidally stable nanocubes. Second, we elucidate the pathway by which copper(II) nitrate and oleylamine form Cu3N. We find that oleylamine is both a reductant and a nitrogen source. Oleylamine is oxidized by nitrate to a primary aldimine, which reacts further with excess oleylamine to a secondary aldimine, eliminating ammonia. Ammonia reacts with CuI to form Cu3N. Third, we investigated the surface chemistry and find a mixed ligand shell of aliphatic amines and carboxylates (formed in situ). While the carboxylates appear tightly bound, the amines are easily desorbed from the surface. Finally, we show that doping with palladium decreases the band gap and the material becomes semi-metallic. These results bring insight into the chemistry of metal nitrides and might help the development of other metal nitride nanocrystals.
AU - Parvizian, Mahsa
AU - Duràn Balsa, Alejandra
AU - Pokratath, Rohan
AU - Kalha, Curran
AU - Lee, Seungho
AU - Van Den Eynden, Dietger
AU - Ibáñez, Maria
AU - Regoutz, Anna
AU - De Roo, Jonathan
ID - 11451
IS - 31
JF - Angewandte Chemie - International Edition
SN - 1433-7851
TI - The chemistry of Cu₃N and Cu₃PdN nanocrystals
VL - 61
ER -
TY - JOUR
AB - A novel multivariable system, combining a transistor with fiber optic-based surface plasmon resonance spectroscopy with the gate electrode simultaneously acting as the fiber optic sensor surface, is reported. The dual-mode sensor allows for discrimination of mass and charge contributions for binding assays on the same sensor surface. Furthermore, we optimize the sensor geometry by investigating the influence of the fiber area to transistor channel area ratio and distance. We show that larger fiber optic tip diameters are favorable for electronic and optical signals and demonstrate the reversibility of plasmon resonance wavelength shifts after electric field application. As a proof of principle, a layer-by-layer assembly of polyelectrolytes is performed to benchmark the system against multivariable sensing platforms with planar surface plasmon resonance configurations. Furthermore, the biosensing performance is assessed using a thrombin binding assay with surface-immobilized aptamers as receptors, allowing for the detection of medically relevant thrombin concentrations.
AU - Hasler, Roger
AU - Reiner-Rozman, Ciril
AU - Fossati, Stefan
AU - Aspermair, Patrik
AU - Dostalek, Jakub
AU - Lee, Seungho
AU - Ibáñez, Maria
AU - Bintinger, Johannes
AU - Knoll, Wolfgang
ID - 10829
IS - 2
JF - ACS Sensors
TI - Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device
VL - 7
ER -
TY - JOUR
AB - In Fall 2020, several European countries reported rapid increases in COVID-19 cases along with growing estimates of the effective reproduction rates. Such an acceleration in epidemic spread is usually attributed to time-dependent effects, e.g. human travel, seasonal behavioral changes, mutations of the pathogen etc. In this case however the acceleration occurred when counter measures such as testing and contact tracing exceeded their capacity limit. Considering Austria as an example, here we show that this dynamics can be captured by a time-independent, i.e. autonomous, compartmental model that incorporates these capacity limits. In this model, the epidemic acceleration coincides with the exhaustion of mitigation efforts, resulting in an increasing fraction of undetected cases that drive the effective reproduction rate progressively higher. We demonstrate that standard models which does not include this effect necessarily result in a systematic underestimation of the effective reproduction rate.
AU - Budanur, Nazmi B
AU - Hof, Björn
ID - 11704
IS - 7
JF - PLoS ONE
TI - An autonomous compartmental model for accelerating epidemics
VL - 17
ER -
TY - GEN
AB - Maternally inherited Wolbachia transinfections are being introduced into natural mosquito populations to reduce the transmission of dengue, Zika and other arboviruses. Wolbachia-induced cytoplasmic incompatibility provides a frequency-dependent reproductive advantage to infected females that can spread transinfections within and among populations. However, because transinfections generally reduce host fitness, they tend to spread within populations only after their frequency exceeds a critical threshold. This produces bistability with stable equilibrium frequencies at both 0 and 1, analogous to the bistability produced by underdominance between alleles or karyotypes and by population dynamics under Allee effects. Here, we analyze how stochastic frequency variation produced by finite population size can facilitate the local spread of variants with bistable dynamics into areas where invasion is unexpected from deterministic models. Our exemplar is the establishment of wMel Wolbachia in the Aedes aegypti population of Pyramid Estates (PE), a small community in far north Queensland, Australia. In 2011, wMel was stably introduced into Gordonvale, separated from PE by barriers to Ae. aegypti dispersal. After nearly six years during which wMel was observed only at low frequencies in PE, corresponding to an apparent equilibrium between immigration and selection, wMel rose to fixation by 2018. Using analytic approximations and statistical analyses, we demonstrate that the observed fixation of wMel at PE is consistent with both stochastic transition past an unstable threshold frequency and deterministic transformation produced by steady immigration at a rate just above the threshold required for deterministic invasion. The indeterminacy results from a delicate balance of parameters needed to produce the delayed transition observed. Our analyses suggest that once Wolbachia transinfections are established locally through systematic introductions, stochastic “threshold crossing” is likely to only minimally enhance spatial spread, providing a local ratchet that slightly – but systematically – aids area-wide transformation of disease-vector populations in heterogeneous landscapes.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 11686
KW - Biological sciences
TI - Wolbachia frequency data from: Why did the Wolbachia transinfection cross the road? Drift, deterministic dynamics and disease control
ER -
TY - GEN
AB - Detailed information about the data set see "dataset description.txt" file.
AU - Hasler, Roger
AU - Reiner-Rozman, Ciril
AU - Fossati, Stefan
AU - Aspermair, Patrik
AU - Dostalek, Jakub
AU - Lee, Seungho
AU - Ibáñez, Maria
AU - Bintinger, Johannes
AU - Knoll, Wolfgang
ID - 10833
TI - Field-effect transistor with a plasmonic fiber optic gate electrode as a multivariable biosensor device
ER -
TY - GEN
AB - Data underlying the figures in the publication "The chemistry of Cu3N and Cu3PdN nanocrystals"
AU - Parvizian, Mahsa
AU - Duran Balsa, Alejandra
AU - Pokratath, Rohan
AU - Kalha, Curran
AU - Lee, Seungho
AU - Van den Eynden, Dietger
AU - Ibáñez, Maria
AU - Regoutz, Anna
AU - De Roo, Jonathan
ID - 11695
TI - Data for "The chemistry of Cu3N and Cu3PdN nanocrystals"
ER -
TY - GEN
AB - Codes and data for reproducing the results of N. B. Budanur and B. Hof "An autonomous compartmental model for accelerating epidemics"
AU - Budanur, Nazmi B
ID - 11711
TI - burakbudanur/autoacc-public
ER -
TY - CONF
AB - We consider the quantitative problem of obtaining lower-bounds on the probability of termination of a given non-deterministic probabilistic program. Specifically, given a non-termination threshold p∈[0,1], we aim for certificates proving that the program terminates with probability at least 1−p. The basic idea of our approach is to find a terminating stochastic invariant, i.e. a subset SI of program states such that (i) the probability of the program ever leaving SI is no more than p, and (ii) almost-surely, the program either leaves SI or terminates.
While stochastic invariants are already well-known, we provide the first proof that the idea above is not only sound, but also complete for quantitative termination analysis. We then introduce a novel sound and complete characterization of stochastic invariants that enables template-based approaches for easy synthesis of quantitative termination certificates, especially in affine or polynomial forms. Finally, by combining this idea with the existing martingale-based methods that are relatively complete for qualitative termination analysis, we obtain the first automated, sound, and relatively complete algorithm for quantitative termination analysis. Notably, our completeness guarantees for quantitative termination analysis are as strong as the best-known methods for the qualitative variant.
Our prototype implementation demonstrates the effectiveness of our approach on various probabilistic programs. We also demonstrate that our algorithm certifies lower bounds on termination probability for probabilistic programs that are beyond the reach of previous methods.
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir Kafshdar
AU - Meggendorfer, Tobias
AU - Zikelic, Dorde
ID - 12000
SN - 0302-9743
T2 - Proceedings of the 34th International Conference on Computer Aided Verification
TI - Sound and complete certificates for auantitative termination analysis of probabilistic programs
VL - 13371
ER -
TY - JOUR
AB - Recently it became possible to study highly excited rotational states of molecules in superfluid helium through nonadiabatic alignment experiments (Cherepanov et al 2021 Phys. Rev. A 104 L061303). This calls for theoretical approaches that go beyond explaining renormalized values of molecular spectroscopic constants, which suffices when only the lowest few rotational states are involved. As the first step in this direction, here we present a basic quantum mechanical model describing highly excited rotational states of molecules in superfluid helium nanodroplets. We show that a linear molecule immersed in a superfluid can be seen as an effective symmetric top, similar to the rotational structure of radicals, such as OH or NO, but with the angular momentum of the superfluid playing the role of the electronic angular momentum in free molecules. The simple theory sheds light onto what happens when the rotational angular momentum of the molecule increases beyond the lowest excited states accessible by infrared spectroscopy. In addition, the model allows to estimate the effective rotational and centrifugal distortion constants for a broad range of species and to explain the crossover between light and heavy molecules in superfluid 4He in terms of the many-body wavefunction structure. Some of the above mentioned insights can be acquired by analyzing a simple 2 × 2 matrix.
AU - Cherepanov, Igor
AU - Bighin, Giacomo
AU - Schouder, Constant A.
AU - Chatterley, Adam S.
AU - Stapelfeldt, Henrik
AU - Lemeshko, Mikhail
ID - 11998
IS - 7
JF - New Journal of Physics
SN - 1367-2630
TI - A simple model for high rotational excitations of molecules in a superfluid
VL - 24
ER -
TY - JOUR
AB - Sexual antagonism is a common hypothesis for driving the evolution of sex chromosomes, whereby recombination suppression is favored between sexually antagonistic loci and the sex-determining locus to maintain beneficial combinations of alleles. This results in the formation of a sex-determining region. Chromosomal inversions may contribute to recombination suppression but their precise role in sex chromosome evolution remains unclear. Because local adaptation is frequently facilitated through the suppression of recombination between adaptive loci by chromosomal inversions, there is potential for inversions that cover sex-determining regions to be involved in local adaptation as well, particularly if habitat variation creates environment-dependent sexual antagonism. With these processes in mind, we investigated sex determination in a well-studied example of local adaptation within a species: the intertidal snail, Littorina saxatilis. Using SNP data from a Swedish hybrid zone, we find novel evidence for a female-heterogametic sex determination system that is restricted to one ecotype. Our results suggest that four putative chromosomal inversions, two previously described and two newly discovered, span the putative sex chromosome pair. We determine their differing associations with sex, which suggest distinct strata of differing ages. The same inversions are found in the second ecotype but do not show any sex association. The striking disparity in inversion-sex associations between ecotypes that are connected by gene flow across a habitat transition that is just a few meters wide indicates a difference in selective regime that has produced a distinct barrier to the spread of the newly discovered sex-determining region between ecotypes. Such sex chromosome-environment interactions have not previously been uncovered in L. saxatilis and are known in few other organisms. A combination of both sex-specific selection and divergent natural selection is required to explain these highly unusual patterns.
AU - Hearn, Katherine E.
AU - Koch, Eva L.
AU - Stankowski, Sean
AU - Butlin, Roger K.
AU - Faria, Rui
AU - Johannesson, Kerstin
AU - Westram, Anja M
ID - 12001
JF - Evolution Letters
TI - Differing associations between sex determination and sex-linked inversions in two ecotypes of Littorina saxatilis
ER -
TY - JOUR
AB - A simple drawing D(G) of a graph G is one where each pair of edges share at most one point: either a common endpoint or a proper crossing. An edge e in the complement of G can be inserted into D(G) if there exists a simple drawing of G+e extending D(G). As a result of Levi’s Enlargement Lemma, if a drawing is rectilinear (pseudolinear), that is, the edges can be extended into an arrangement of lines (pseudolines), then any edge in the complement of G can be inserted. In contrast, we show that it is NP-complete to decide whether one edge can be inserted into a simple drawing. This remains true even if we assume that the drawing is pseudocircular, that is, the edges can be extended to an arrangement of pseudocircles. On the positive side, we show that, given an arrangement of pseudocircles A and a pseudosegment σ, it can be decided in polynomial time whether there exists a pseudocircle Φσ extending σ for which A∪{Φσ} is again an arrangement of pseudocircles.
AU - Arroyo Guevara, Alan M
AU - Klute, Fabian
AU - Parada, Irene
AU - Vogtenhuber, Birgit
AU - Seidel, Raimund
AU - Wiedera, Tilo
ID - 11999
JF - Discrete and Computational Geometry
SN - 0179-5376
TI - Inserting one edge into a simples drawing is hard
ER -
TY - JOUR
AB - G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.
AU - Schulz, Rouven
AU - Korkut, Medina
AU - Venturino, Alessandro
AU - Colombo, Gloria
AU - Siegert, Sandra
ID - 11995
JF - Nature Communications
TI - Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
VL - 13
ER -
TY - THES
AB - G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.
We validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.
Our DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level.
AU - Schulz, Rouven
ID - 11945
SN - 2663-337X
TI - Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function
ER -
TY - DATA
AU - Schulz, Rouven
ID - 11542
TI - Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses)
ER -
TY - JOUR
AB - Interlocking puzzles are intriguing geometric games where the puzzle pieces are held together based on their geometric arrangement, preventing the puzzle from falling apart. High-level-of-difficulty, or simply high-level, interlocking puzzles are a subclass of interlocking puzzles that require multiple moves to take out the first subassembly from the puzzle. Solving a high-level interlocking puzzle is a challenging task since one has to explore many different configurations of the puzzle pieces until reaching a configuration where the first subassembly can be taken out. Designing a high-level interlocking puzzle with a user-specified level of difficulty is even harder since the puzzle pieces have to be interlocking in all the configurations before the first subassembly is taken out.
In this paper, we present a computational approach to design high-level interlocking puzzles. The core idea is to represent all possible configurations of an interlocking puzzle as well as transitions among these configurations using a rooted, undirected graph called a disassembly graph and leverage this graph to find a disassembly plan that requires a minimal number of moves to take out the first subassembly from the puzzle. At the design stage, our algorithm iteratively constructs the geometry of each puzzle piece to expand the disassembly graph incrementally, aiming to achieve a user-specified level of difficulty. We show that our approach allows efficient generation of high-level interlocking puzzles of various shape complexities, including new solutions not attainable by state-of-the-art approaches.
AU - Chen, Rulin
AU - Wang, Ziqi
AU - Song, Peng
AU - Bickel, Bernd
ID - 11735
IS - 4
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - Computational design of high-level interlocking puzzles
VL - 41
ER -
TY - JOUR
AB - We study the fate of an impurity in an ultracold heteronuclear Bose mixture, focusing on the experimentally relevant case of a ⁴¹K - ⁸⁷Rb mixture, with the impurity in a ⁴¹K hyperfine state. Our paper provides a comprehensive description of an impurity in a BEC mixture with contact interactions across its phase diagram. We present results for the miscible and immiscible regimes, as well as for the impurity in a self-bound quantum droplet. Here, varying the interactions, we find exotic states where the impurity localizes either at the center or
at the surface of the droplet.
AU - Bighin, Giacomo
AU - Burchianti, A.
AU - Minardi, F.
AU - Macrì, T.
ID - 11997
IS - 2
JF - Physical Review A
SN - 2469-9926
TI - Impurity in a heteronuclear two-component Bose mixture
VL - 106
ER -
TY - JOUR
AB - If you mix fruit syrups with alcohol to make a schnapps, the two liquids will remain perfectly blended forever. But if you mix oil with vinegar to make a vinaigrette, the oil and vinegar will soon separate back into their previous selves. Such liquid-liquid phase separation is a thermodynamically driven phenomenon and plays an important role in many biological processes (1). Although energy injection at the macroscale can reverse the phase separation—a strong shake is the normal response to a separated vinaigrette—little is known about the effect of energy added at the microscopic level on phase separation. This fundamental question has deep ramifications, notably in biology, because active processes also make the interior of a living cell different from a dead one. On page 768 of this issue, Adkins et al. (2) examine how mechanical activity at the microscopic scale affects liquid-liquid phase separation and allows liquids to climb surfaces.
AU - Palacci, Jérémie A
ID - 11996
IS - 6607
JF - Science
SN - 0036-8075
TI - A soft active matter that can climb walls
VL - 377
ER -
TY - JOUR
AB - The study of the complexity of the constraint satisfaction problem (CSP), centred around the Feder-Vardi Dichotomy Conjecture, has been very prominent in the last two decades. After a long concerted effort and many partial results, the Dichotomy Conjecture has been proved in 2017 independently by Bulatov and Zhuk. At about the same time, a vast generalisation of CSP, called promise CSP, has started to gain prominence. In this survey, we explain the importance of promise CSP and highlight many new very interesting features that the study of promise CSP has brought to light. The complexity classification quest for the promise CSP is wide open, and we argue that, despite the promise CSP being more general, this quest is rather more accessible to a wide range of researchers than the dichotomy-led study of the CSP has been.
AU - Krokhin, Andrei
AU - Opršal, Jakub
ID - 11991
IS - 3
JF - ACM SIGLOG News
SN - 2372-3491
TI - An invitation to the promise constraint satisfaction problem
VL - 9
ER -
TY - JOUR
AB - Changes in the short-term dynamics of excitatory synapses over development have been observed throughout cortex, but their purpose and consequences remain unclear. Here, we propose that developmental changes in synaptic dynamics buffer the effect of slow inhibitory long-term plasticity, allowing for continuously stable neural activity. Using computational modeling we demonstrate that early in development excitatory short-term depression quickly stabilises neural activity, even in the face of strong, unbalanced excitation. We introduce a model of the commonly observed developmental shift from depression to facilitation and show that neural activity remains stable throughout development, while inhibitory synaptic plasticity slowly balances excitation, consistent with experimental observations. Our model predicts changes in the input responses from phasic to phasic-and-tonic and more precise spike timings. We also observe a gradual emergence of short-lasting memory traces governed by short-term plasticity development. We conclude that the developmental depression-to-facilitation shift may control excitation-inhibition balance throughout development with important functional consequences.
AU - Jia, David W.
AU - Vogels, Tim P
AU - Costa, Rui Ponte
ID - 12009
JF - Communications biology
TI - Developmental depression-to-facilitation shift controls excitation-inhibition balance
VL - 5
ER -
TY - CONF
AB - World models learn behaviors in a latent imagination space to enhance the sample-efficiency of deep reinforcement learning (RL) algorithms. While learning world models for high-dimensional observations (e.g., pixel inputs) has become practicable on standard RL benchmarks and some games, their effectiveness in real-world robotics applications has not been explored. In this paper, we investigate how such agents generalize to real-world autonomous vehicle control tasks, where advanced model-free deep RL algorithms fail. In particular, we set up a series of time-lap tasks for an F1TENTH racing robot, equipped with a high-dimensional LiDAR sensor, on a set of test tracks with a gradual increase in their complexity. In this continuous-control setting, we show that model-based agents capable of learning in imagination substantially outperform model-free agents with respect to performance, sample efficiency, successful task completion, and generalization. Moreover, we show that the generalization ability of model-based agents strongly depends on the choice of their observation model. We provide extensive empirical evidence for the effectiveness of world models provided with long enough memory horizons in sim2real tasks.
AU - Brunnbauer, Axel
AU - Berducci, Luigi
AU - Brandstatter, Andreas
AU - Lechner, Mathias
AU - Hasani, Ramin
AU - Rus, Daniela
AU - Grosu, Radu
ID - 12010
SN - 1050-4729
T2 - 2022 International Conference on Robotics and Automation
TI - Latent imagination facilitates zero-shot transfer in autonomous racing
ER -
TY - CONF
AB - We consider the problem of communication over adversarial channels with feedback. Two parties comprising sender Alice and receiver Bob seek to communicate reliably. An adversary James observes Alice's channel transmission entirely and chooses, maliciously, its additive channel input or jamming state thereby corrupting Bob's observation. Bob can communicate over a one-way reverse link with Alice; we assume that transmissions over this feedback link cannot be corrupted by James. Our goal in this work is to study the optimum throughput or capacity over such channels with feedback. We first present results for the quadratically-constrained additive channel where communication is known to be impossible when the noise-to-signal (power) ratio (NSR) is at least 1. We present a novel achievability scheme to establish that positive rate communication is possible even when the NSR is as high as 8/9. We also present new converse upper bounds on the capacity of this channel under potentially stochastic encoders and decoders. We also study feedback communication over the more widely studied q-ary alphabet channel under additive noise. For the q -ary channel, where q > 2, it is well known that capacity is positive under full feedback if and only if the adversary can corrupt strictly less than half the transmitted symbols. We generalize this result and show that the same threshold holds for positive rate communication when the noiseless feedback may only be partial; our scheme employs a stochastic decoder. We extend this characterization, albeit partially, to fully deterministic schemes under partial noiseless feedback. We also present new converse upper bounds for q-ary channels under full feedback, where the encoder and/or decoder may privately randomize. Our converse results bring to the fore an interesting alternate expression for the well known converse bound for the q—ary channel under full feedback which, when specialized to the binary channel, also equals its known capacity.
AU - Joshi, Pranav
AU - Purkayastha, Amritakshya
AU - Zhang, Yihan
AU - Budkuley, Amitalok J.
AU - Jaggi, Sidharth
ID - 12013
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - On the capacity of additive AVCs with feedback
VL - 2022
ER -
TY - CONF
AB - We consider the problem of coded distributed computing using polar codes. The average execution time of a coded computing system is related to the error probability for transmission over the binary erasure channel in recent work by Soleymani, Jamali and Mahdavifar, where the performance of binary linear codes is investigated. In this paper, we focus on polar codes and unveil a connection between the average execution time and the scaling exponent μ of the family of codes. In the finite-length characterization of polar codes, the scaling exponent is a key object capturing the speed of convergence to capacity. In particular, we show that (i) the gap between the normalized average execution time of polar codes and that of optimal MDS codes is O(n –1/μ ), and (ii) this upper bound can be improved to roughly O(n –1/2 ) by considering polar codes with large kernels. We conjecture that these bounds could be improved to O(n –2/μ ) and O(n –1 ), respectively, and provide a heuristic argument as well as numerical evidence supporting this view.
AU - Fathollahi, Dorsa
AU - Mondelli, Marco
ID - 12016
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - Polar coded computing: The role of the scaling exponent
VL - 2022
ER -
TY - CONF
AB - This paper is eligible for the Jack Keil Wolf ISIT Student Paper Award. We generalize a previous framework for designing utility-optimal differentially private (DP) mechanisms via graphs, where datasets are vertices in the graph and edges represent dataset neighborhood. The boundary set contains datasets where an individual’s response changes the binary-valued query compared to its neighbors. Previous work was limited to the homogeneous case where the privacy parameter ε across all datasets was the same and the mechanism at boundary datasets was identical. In our work, the mechanism can take different distributions at the boundary and the privacy parameter ε is a function of neighboring datasets, which recovers an earlier definition of personalized DP as special case. The problem is how to extend the mechanism, which is only defined at the boundary set, to other datasets in the graph in a computationally efficient and utility optimal manner. Using the concept of strongest induced DP condition we solve this problem efficiently in polynomial time (in the size of the graph).
AU - Torkamani, Sahel
AU - Ebrahimi, Javad B.
AU - Sadeghi, Parastoo
AU - D'Oliveira, Rafael G.L.
AU - Médard, Muriel
ID - 12012
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - Heterogeneous differential privacy via graphs
VL - 2022
ER -
TY - CONF
AB - We characterize the capacity for the discrete-time arbitrarily varying channel with discrete inputs, outputs, and states when (a) the encoder and decoder do not share common randomness, (b) the input and state are subject to cost constraints, (c) the transition matrix of the channel is deterministic given the state, and (d) at each time step the adversary can only observe the current and past channel inputs when choosing the state at that time. The achievable strategy involves stochastic encoding together with list decoding and a disambiguation step. The converse uses a two-phase "babble-and-push" strategy where the adversary chooses the state randomly in the first phase, list decodes the output, and then chooses state inputs to symmetrize the channel in the second phase. These results generalize prior work on specific channels models (additive, erasure) to general discrete alphabets and models.
AU - Zhang, Yihan
AU - Jaggi, Sidharth
AU - Langberg, Michael
AU - Sarwate, Anand D.
ID - 12011
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - The capacity of causal adversarial channels
VL - 2022
ER -
TY - CONF
AB - We study the problem of high-dimensional multiple packing in Euclidean space. Multiple packing is a natural generalization of sphere packing and is defined as follows. Let P, N > 0 and L∈Z≥2. A multiple packing is a set C of points in Bn(0–,nP−−−√) such that any point in ℝ n lies in the intersection of at most L – 1 balls of radius nN−−−√ around points in C. 1 In this paper, we derive two lower bounds on the largest possible density of a multiple packing. These bounds are obtained through a stronger notion called average-radius multiple packing. Specifically, we exactly pin down the asymptotics of (expurgated) Gaussian codes and (expurgated) spherical codes under average-radius multiple packing. To this end, we apply tools from high-dimensional geometry and large deviation theory. The bound for spherical codes matches the previous best known bound which was obtained for the standard (weaker) notion of multiple packing through a curious connection with error exponents [Bli99], [ZV21]. The bound for Gaussian codes suggests that they are strictly inferior to spherical codes.
AU - Zhang, Yihan
AU - Vatedka, Shashank
ID - 12015
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - Lower bounds for multiple packing
VL - 2022
ER -
TY - CONF
AB - We study the problem of high-dimensional multiple packing in Euclidean space. Multiple packing is a natural generalization of sphere packing and is defined as follows. Let N > 0 and L∈Z≥2. A multiple packing is a set C of points in Rn such that any point in Rn lies in the intersection of at most L – 1 balls of radius nN−−−√ around points in C. Given a well-known connection with coding theory, multiple packings can be viewed as the Euclidean analog of list-decodable codes, which are well-studied for finite fields. In this paper, we exactly pin down the asymptotic density of (expurgated) Poisson Point Processes under a stronger notion called average-radius multiple packing. To this end, we apply tools from high-dimensional geometry and large deviation theory. This gives rise to the best known lower bound on the largest multiple packing density. Our result corrects a mistake in a previous paper by Blinovsky [Bli05].
AU - Zhang, Yihan
AU - Vatedka, Shashank
ID - 12014
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - List-decodability of Poisson Point Processes
VL - 2022
ER -
TY - JOUR
AB - Neuronal networks encode information through patterns of activity that define the networks’ function. The neurons’ activity relies on specific connectivity structures, yet the link between structure and function is not fully understood. Here, we tackle this structure-function problem with a new conceptual approach. Instead of manipulating the connectivity directly, we focus on upper triangular matrices, which represent the network dynamics in a given orthonormal basis obtained by the Schur decomposition. This abstraction allows us to independently manipulate the eigenspectrum and feedforward structures of a connectivity matrix. Using this method, we describe a diverse repertoire of non-normal transient amplification, and to complement the analysis of the dynamical regimes, we quantify the geometry of output trajectories through the effective rank of both the eigenvector and the dynamics matrices. Counter-intuitively, we find that shrinking the eigenspectrum’s imaginary distribution leads to highly amplifying regimes in linear and long-lasting dynamics in nonlinear networks. We also find a trade-off between amplification and dimensionality of neuronal dynamics, i.e., trajectories in neuronal state-space. Networks that can amplify a large number of orthogonal initial conditions produce neuronal trajectories that lie in the same subspace of the neuronal state-space. Finally, we examine networks of excitatory and inhibitory neurons. We find that the strength of global inhibition is directly linked with the amplitude of amplification, such that weakening inhibitory weights also decreases amplification, and that the eigenspectrum’s imaginary distribution grows with an increase in the ratio between excitatory-to-inhibitory and excitatory-to-excitatory connectivity strengths. Consequently, the strength of global inhibition reveals itself as a strong signature for amplification and a potential control mechanism to switch dynamical regimes. Our results shed a light on how biological networks, i.e., networks constrained by Dale’s law, may be optimised for specific dynamical regimes.
AU - Christodoulou, Georgia
AU - Vogels, Tim P
AU - Agnes, Everton J.
ID - 12084
IS - 8
JF - PLoS Computational Biology
TI - Regimes and mechanisms of transient amplification in abstract and biological neural networks
VL - 18
ER -
TY - DATA
AB - FtsA is crucial for assembly of the E. coli divisome, as it dynamically links cytoplasmic FtsZ filaments with transmembrane cell division proteins. FtsA allegedly initiates cell division by switching from an inactive polymeric to an active monomeric confirmation, which recruits downstream proteins and stabilizes FtsZ filaments. Here, we use biochemical reconstitution experiments combined with quantitative fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing FtsZ filaments and recruiting FtsN. We attribute these differences to a faster membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments. Using FRET microscopy, we find that FtsN binding does not compete with, but promotes FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic polymers on the membrane, which re-organize during assembly and activation of the divisome.
AU - Radler, Philipp
ID - 10934
KW - Bacterial cell division
KW - in vitro reconstitution
KW - FtsZ
KW - FtsN
KW - FtsA
TI - In vitro reconstitution of Escherichia coli divisome activation
ER -
TY - JOUR
AB - The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ.
AU - Radler, Philipp
AU - Baranova, Natalia S.
AU - Dos Santos Caldas, Paulo R
AU - Sommer, Christoph M
AU - Lopez Pelegrin, Maria D
AU - Michalik, David
AU - Loose, Martin
ID - 11373
JF - Nature Communications
KW - General Physics and Astronomy
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Chemistry
SN - 2041-1723
TI - In vitro reconstitution of Escherichia coli divisome activation
VL - 13
ER -
TY - JOUR
AB - Calcium-dependent protein kinases (CPK) are key components of a wide array of signaling pathways, translating stress and nutrient signaling into the modulation of cellular processes such as ion transport and transcription. However, not much is known about CPKs in endomembrane trafficking. Here, we screened for CPKs that impact on root growth and gravitropism, by overexpressing constitutively active forms of CPKs under the control of an inducible promoter in Arabidopsis thaliana. We found that inducible overexpression of an constitutive active CPK30 (CA-CPK30) resulted in a loss of root gravitropism and ectopic auxin accumulation in the root tip. Immunolocalization revealed that CA-CPK30 roots have reduced PIN protein levels, PIN1 polarity defects and impaired Brefeldin A (BFA)-sensitive trafficking. Moreover, FM4-64 uptake was reduced, indicative of a defect in endocytosis. The effects on BFA-sensitive trafficking were not specific to PINs, as BFA could not induce aggregation of ARF1- and CHC-labeled endosomes in CA-CPK30. Interestingly, the interference with BFA-body formation, could be reverted by increasing the extracellular pH, indicating a pH-dependence of this CA-CPK30 effect. Altogether, our data reveal an important role for CPK30 in root growth regulation and endomembrane trafficking in Arabidopsis thaliana.
AU - Wang, Ren
AU - Himschoot, Ellie
AU - Chen, Jian
AU - Boudsocq, Marie
AU - Geelen, Danny
AU - Friml, Jiří
AU - Beeckman, Tom
AU - Vanneste, Steffen
ID - 11589
JF - Frontiers in Plant Science
TI - Constitutive active CPK30 interferes with root growth and endomembrane trafficking in Arabidopsis thaliana
VL - 13
ER -
TY - JOUR
AB - In holomorphic dynamics, complex box mappings arise as first return maps to wellchosen domains. They are a generalization of polynomial-like mapping, where the domain of the return map can have infinitely many components. They turned out to be extremely useful in tackling diverse problems. The purpose of this paper is:
• To illustrate some pathologies that can occur when a complex box mapping is not induced by a globally defined map and when its domain has infinitely many components, and to give conditions to avoid these issues.
• To show that once one has a box mapping for a rational map, these conditions can be assumed to hold in a very natural setting. Thus, we call such complex box mappings dynamically natural. Having such box mappings is the first step in tackling many problems in one-dimensional dynamics.
• Many results in holomorphic dynamics rely on an interplay between combinatorial and analytic techniques. In this setting, some of these tools are:
• the Enhanced Nest (a nest of puzzle pieces around critical points) from Kozlovski, Shen, van Strien (AnnMath 165:749–841, 2007), referred to below as KSS;
• the Covering Lemma (which controls the moduli of pullbacks of annuli) from Kahn and Lyubich (Ann Math 169(2):561–593, 2009);
• the QC-Criterion and the Spreading Principle from KSS.
The purpose of this paper is to make these tools more accessible so that they can be used as a ‘black box’, so one does not have to redo the proofs in new settings.
• To give an intuitive, but also rather detailed, outline of the proof from KSS and Kozlovski and van Strien (Proc Lond Math Soc (3) 99:275–296, 2009) of the following results for non-renormalizable dynamically natural complex box mappings:
• puzzle pieces shrink to points,
• (under some assumptions) topologically conjugate non-renormalizable polynomials and box mappings are quasiconformally conjugate.
• We prove the fundamental ergodic properties for dynamically natural box mappings. This leads to some necessary conditions for when such a box mapping supports a measurable invariant line field on its filled Julia set. These mappings
are the analogues of Lattès maps in this setting.
• We prove a version of Mañé’s Theorem for complex box mappings concerning expansion along orbits of points that avoid a neighborhood of the set of critical points.
AU - Clark, Trevor
AU - Drach, Kostiantyn
AU - Kozlovski, Oleg
AU - Strien, Sebastian Van
ID - 11553
IS - 2
JF - Arnold Mathematical Journal
SN - 2199-6792
TI - The dynamics of complex box mappings
VL - 8
ER -
TY - THES
AB - In this thesis, we study two of the most important questions in Arithmetic geometry: that of the existence and density of solutions to Diophantine equations. In order for a Diophantine equation to have any solutions over the rational numbers, it must have solutions everywhere locally, i.e., over R and over Qp for every prime p. The converse, called the Hasse principle, is known to fail in general. However, it is still a central question in Arithmetic geometry to determine for which varieties the Hasse principle does hold. In this work, we establish the Hasse principle for a wide new family of varieties of the form f(t) = NK/Q(x) ̸= 0, where f is a polynomial with integer coefficients and NK/Q denotes the norm
form associated to a number field K. Our results cover products of arbitrarily many linear, quadratic or cubic factors, and generalise an argument of Irving [69], which makes use of the beta sieve of Rosser and Iwaniec. We also demonstrate how our main sieve results can be applied to treat new cases of a conjecture of Harpaz and Wittenberg on locally split values of polynomials over number fields, and discuss consequences for rational points in fibrations.
In the second question, about the density of solutions, one defines a height function and seeks to estimate asymptotically the number of points of height bounded by B as B → ∞. Traditionally, one either counts rational points, or
integral points with respect to a suitable model. However, in this thesis, we study an emerging area of interest in Arithmetic geometry known as Campana points, which in some sense interpolate between rational and integral points.
More precisely, we count the number of nonzero integers z1, z2, z3 such that gcd(z1, z2, z3) = 1, and z1, z2, z3, z1 + z2 + z3 are all squareful and bounded by B. Using the circle method, we obtain an asymptotic formula which agrees in
the power of B and log B with a bold new generalisation of Manin’s conjecture to the setting of Campana points, recently formulated by Pieropan, Smeets, Tanimoto and Várilly-Alvarado [96]. However, in this thesis we also provide the first known counterexamples to leading constant predicted by their conjecture.
AU - Shute, Alec L
ID - 12072
SN - 2663-337X
TI - Existence and density problems in Diophantine geometry: From norm forms to Campana points
ER -
TY - JOUR
AB - We consider the many-body time evolution of weakly interacting bosons in the mean field regime for initial coherent states. We show that bounded k-particle operators, corresponding to dependent random variables, satisfy both a law of large numbers and a central limit theorem.
AU - Rademacher, Simone Anna Elvira
ID - 12083
IS - 8
JF - Journal of Mathematical Physics
SN - 0022-2488
TI - Dependent random variables in quantum dynamics
VL - 63
ER -
TY - JOUR
AB - Plant cell growth responds rapidly to various stimuli, adapting architecture to environmental changes. Two major endogenous signals regulating growth are the phytohormone auxin and the secreted peptides rapid alkalinization factors (RALFs). Both trigger very rapid cellular responses and also exert long-term effects [Du et al., Annu. Rev. Plant Biol. 71, 379–402 (2020); Blackburn et al., Plant Physiol. 182, 1657–1666 (2020)]. However, the way, in which these distinct signaling pathways converge to regulate growth, remains unknown. Here, using vertical confocal microscopy combined with a microfluidic chip, we addressed the mechanism of RALF action on growth. We observed correlation between RALF1-induced rapid Arabidopsis thaliana root growth inhibition and apoplast alkalinization during the initial phase of the response, and revealed that RALF1 reversibly inhibits primary root growth through apoplast alkalinization faster than within 1 min. This rapid apoplast alkalinization was the result of RALF1-induced net H+ influx and was mediated by the receptor FERONIA (FER). Furthermore, we investigated the cross-talk between RALF1 and the auxin signaling pathways during root growth regulation. The results showed that RALF-FER signaling triggered auxin signaling with a delay of approximately 1 h by up-regulating auxin biosynthesis, thus contributing to sustained RALF1-induced growth inhibition. This biphasic RALF1 action on growth allows plants to respond rapidly to environmental stimuli and also reprogram growth and development in the long term.
AU - Li, Lanxin
AU - Chen, Huihuang
AU - Alotaibi, Saqer S.
AU - Pěnčík, Aleš
AU - Adamowski, Maciek
AU - Novák, Ondřej
AU - Friml, Jiří
ID - 11723
IS - 31
JF - Proceedings of the National Academy of Sciences
KW - Multidisciplinary
SN - 0027-8424
TI - RALF1 peptide triggers biphasic root growth inhibition upstream of auxin biosynthesis
VL - 119
ER -
TY - JOUR
AB - We investigate the BCS critical temperature Tc in the high-density limit and derive an asymptotic formula, which strongly depends on the behavior of the interaction potential V on the Fermi-surface. Our results include a rigorous confirmation for the behavior of Tc at high densities proposed by Langmann et al. (Phys Rev Lett 122:157001, 2019) and identify precise conditions under which superconducting domes arise in BCS theory.
AU - Henheik, Sven Joscha
ID - 10623
IS - 1
JF - Mathematical Physics, Analysis and Geometry
KW - geometry and topology
KW - mathematical physics
SN - 1385-0172
TI - The BCS critical temperature at high density
VL - 25
ER -
TY - JOUR
AB - The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior.
AU - Amberg, Nicole
AU - Pauler, Florian
AU - Streicher, Carmen
AU - Hippenmeyer, Simon
ID - 11336
IS - 44
JF - Science Advances
SN - 2375-2548
TI - Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression
VL - 8
ER -
TY - CHAP
AB - The proteomes of specialized structures, and the interactomes of proteins of interest, provide entry points to elucidate the functions of molecular machines. Here, we review a proximity-labeling strategy that uses the improved E. coli biotin ligase TurboID to characterize C. elegans protein complexes. Although the focus is on C. elegans neurons, the method is applicable regardless of cell type. We describe detailed extraction procedures that solubilize the bulk of C. elegans proteins and highlight the importance of tagging endogenous genes, to ensure physiological expression levels. We review issues associated with non-specific background noise and the importance of appropriate controls. As proof of principle, we review our analysis of the interactome of a presynaptic active zone protein, ELKS-1. Our aim is to provide a detailed protocol for TurboID-based proximity labeling in C. elegans and to highlight its potential and its limitations to characterize protein complexes and subcellular compartments in this animal.
AU - Artan, Murat
AU - de Bono, Mario
ED - Yamamoto, Daisuke
ID - 11456
SN - 0893-2336
T2 - Behavioral Neurogenetics
TI - Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling
VL - 181
ER -
TY - CONF
AB - It is a highly desirable property for deep networks to be robust against
small input changes. One popular way to achieve this property is by designing
networks with a small Lipschitz constant. In this work, we propose a new
technique for constructing such Lipschitz networks that has a number of
desirable properties: it can be applied to any linear network layer
(fully-connected or convolutional), it provides formal guarantees on the
Lipschitz constant, it is easy to implement and efficient to run, and it can be
combined with any training objective and optimization method. In fact, our
technique is the first one in the literature that achieves all of these
properties simultaneously. Our main contribution is a rescaling-based weight
matrix parametrization that guarantees each network layer to have a Lipschitz
constant of at most 1 and results in the learned weight matrices to be close to
orthogonal. Hence we call such layers almost-orthogonal Lipschitz (AOL).
Experiments and ablation studies in the context of image classification with
certified robust accuracy confirm that AOL layers achieve results that are on
par with most existing methods. Yet, they are simpler to implement and more
broadly applicable, because they do not require computationally expensive
matrix orthogonalization or inversion steps as part of the network
architecture. We provide code at https://github.com/berndprach/AOL.
AU - Prach, Bernd
AU - Lampert, Christoph
ID - 11839
SN - 9783031198021
T2 - Computer Vision – ECCV 2022
TI - Almost-orthogonal layers for efficient general-purpose Lipschitz networks
VL - 13681
ER -
TY - JOUR
AB - In 1998 Burago and Kleiner and (independently) McMullen gave examples of separated nets in Euclidean space which are non-bilipschitz equivalent to the integer lattice. We study weaker notions of equivalence of separated nets and demonstrate that such notions also give rise to distinct equivalence classes. Put differently, we find occurrences of particularly strong divergence of separated nets from the integer lattice. Our approach generalises that of Burago and Kleiner and McMullen which takes place largely in a continuous setting. Existence of irregular separated nets is verified via the existence of non-realisable density functions ρ:[0,1]d→(0,∞). In the present work we obtain stronger types of non-realisable densities.
AU - Dymond, Michael
AU - Kaluza, Vojtech
ID - 9652
JF - Israel Journal of Mathematics
KW - Lipschitz
KW - bilipschitz
KW - bounded displacement
KW - modulus of continuity
KW - separated net
KW - non-realisable density
KW - Burago--Kleiner construction
TI - Highly irregular separated nets
ER -
TY - JOUR
AB - Strigolactones (SLs) are a class of phytohormones that regulate plant shoot branching and adventitious root development. However, little is known regarding the role of SLs in controlling the behavior of the smallest unit of the organism, the single cell. Here, taking advantage of a classic single-cell model offered by the cotton (Gossypium hirsutum) fiber cell, we show that SLs, whose biosynthesis is fine-tuned by gibberellins (GAs), positively regulate cell elongation and cell wall thickness by promoting the biosynthesis of very-long-chain fatty acids (VLCFAs) and cellulose, respectively. Furthermore, we identified two layers of transcription factors (TFs) involved in the hierarchical regulation of this GA-SL crosstalk. The top-layer TF GROWTH-REGULATING FACTOR 4 (GhGRF4) directly activates expression of the SL biosynthetic gene DWARF27 (D27) to increase SL accumulation in fiber cells and GAs induce GhGRF4 expression. SLs induce the expression of four second-layer TF genes (GhNAC100-2, GhBLH51, GhGT2, and GhB9SHZ1), which transmit SL signals downstream to two ketoacyl-CoA synthase genes (KCS) and three cellulose synthase (CesA) genes by directly activating their transcription. Finally, the KCS and CesA enzymes catalyze the biosynthesis of very long chain fatty acids and cellulose, respectively, to regulate development of high-grade cotton fibers. In addition to providing a theoretical basis for cotton fiber improvement, our results shed light on SL signaling in plant development at the single-cell level.
AU - Tian, Z
AU - Zhang, Yuzhou
AU - Zhu, L
AU - Jiang, B
AU - Wang, H
AU - Gao, R
AU - Friml, Jiří
AU - Xiao, G
ID - 12053
IS - 12
JF - The Plant Cell
SN - 1040-4651
TI - Strigolactones act downstream of gibberellins to regulate fiber cell elongation and cell wall thickness in cotton (Gossypium hirsutum)
VL - 34
ER -
TY - JOUR
AB - Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This “dock II” domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor–binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain–containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble.
AU - Daiß, Julia L
AU - Pilsl, Michael
AU - Straub, Kristina
AU - Bleckmann, Andrea
AU - Höcherl, Mona
AU - Heiss, Florian B
AU - Abascal-Palacios, Guillermo
AU - Ramsay, Ewan P
AU - Tluckova, Katarina
AU - Mars, Jean-Clement
AU - Fürtges, Torben
AU - Bruckmann, Astrid
AU - Rudack, Till
AU - Bernecky, Carrie A
AU - Lamour, Valérie
AU - Panov, Konstantin
AU - Vannini, Alessandro
AU - Moss, Tom
AU - Engel, Christoph
ID - 12051
IS - 11
JF - Life Science Alliance
KW - Health
KW - Toxicology and Mutagenesis
KW - Plant Science
KW - Biochemistry
KW - Genetics and Molecular Biology (miscellaneous)
KW - Ecology
SN - 2575-1077
TI - The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans
VL - 5
ER -
TY - CONF
AB - Quantitative monitoring can be universal and approximate: For every finite sequence of observations, the specification provides a value and the monitor outputs a best-effort approximation of it. The quality of the approximation may depend on the resources that are available to the monitor. By taking to the limit the sequences of specification values and monitor outputs, we obtain precision-resource trade-offs also for limit monitoring. This paper provides a formal framework for studying such trade-offs using an abstract interpretation for monitors: For each natural number n, the aggregate semantics of a monitor at time n is an equivalence relation over all sequences of at most n observations so that two equivalent sequences are indistinguishable to the monitor and thus mapped to the same output. This abstract interpretation of quantitative monitors allows us to measure the number of equivalence classes (or “resource use”) that is necessary for a certain precision up to a certain time, or at any time. Our framework offers several insights. For example, we identify a family of specifications for which any resource-optimal exact limit monitor is independent of any error permitted over finite traces. Moreover, we present a specification for which any resource-optimal approximate limit monitor does not minimize its resource use at any time.
AU - Henzinger, Thomas A
AU - Mazzocchi, Nicolas Adrien
AU - Sarac, Naci E
ID - 11775
SN - 0302-9743
T2 - 22nd International Conference on Runtime Verification
TI - Abstract monitors for quantitative specifications
VL - 13498
ER -
TY - JOUR
AB - Directionality in the intercellular transport of the plant hormone auxin is determined by polar plasma membrane localization of PIN-FORMED (PIN) auxin transport proteins. However, apart from PIN phosphorylation at conserved motifs, no further determinants explicitly controlling polar PIN sorting decisions have been identified. Here we present Arabidopsis WAVY GROWTH 3 (WAV3) and closely related RING-finger E3 ubiquitin ligases, whose loss-of-function mutants show a striking apical-to-basal polarity switch in PIN2 localization in root meristem cells. WAV3 E3 ligases function as essential determinants for PIN polarity, acting independently from PINOID/WAG-dependent PIN phosphorylation. They antagonize ectopic deposition of de novo synthesized PIN proteins already immediately following completion of cell division, presumably via preventing PIN sorting into basal, ARF GEF-mediated trafficking. Our findings reveal an involvement of E3 ligases in the selective targeting of apically localized PINs in higher plants.
AU - Konstantinova, N
AU - Hörmayer, Lukas
AU - Glanc, Matous
AU - Keshkeih, R
AU - Tan, Shutang
AU - Di Donato, M
AU - Retzer, K
AU - Moulinier-Anzola, J
AU - Schwihla, M
AU - Korbei, B
AU - Geisler, M
AU - Friml, Jiří
AU - Luschnig, C
ID - 12052
JF - Nature Communications
SN - 2041-1723
TI - WAVY GROWTH Arabidopsis E3 ubiquitin ligases affect apical PIN sorting decisions
VL - 13
ER -
TY - JOUR
AB - Polar auxin transport is unique to plants and coordinates their growth and development1,2. The PIN-FORMED (PIN) auxin transporters exhibit highly asymmetrical localizations at the plasma membrane and drive polar auxin transport3,4; however, their structures and transport mechanisms remain largely unknown. Here, we report three inward-facing conformation structures of Arabidopsis thaliana PIN1: the apo state, bound to the natural auxin indole-3-acetic acid (IAA), and in complex with the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). The transmembrane domain of PIN1 shares a conserved NhaA fold5. In the substrate-bound structure, IAA is coordinated by both hydrophobic stacking and hydrogen bonding. NPA competes with IAA for the same site at the intracellular pocket, but with a much higher affinity. These findings inform our understanding of the substrate recognition and transport mechanisms of PINs and set up a framework for future research on directional auxin transport, one of the most crucial processes underlying plant development.
AU - Yang, Z
AU - Xia, J
AU - Hong, J
AU - Zhang, C
AU - Wei, H
AU - Ying, W
AU - Sun, C
AU - Sun, L
AU - Mao, Y
AU - Gao, Y
AU - Tan, S
AU - Friml, Jiří
AU - Li, D
AU - Liu, X
AU - Sun, L
ID - 12054
IS - 7927
JF - Nature
SN - 0028-0836
TI - Structural insights into auxin recognition and efflux by Arabidopsis PIN1
VL - 609
ER -
TY - CONF
AB - In the classic adversarial communication problem, two parties communicate over a noisy channel in the presence of a malicious jamming adversary. The arbitrarily varying channels (AVCs) offer an elegant framework to study a wide range of interesting adversary models. The optimal throughput or capacity over such AVCs is intimately tied to the underlying adversary model; in some cases, capacity is unknown and the problem is known to be notoriously hard. The omniscient adversary, one which knows the sender’s entire channel transmission a priori, is one of such classic models of interest; the capacity under such an adversary remains an exciting open problem. The myopic adversary is a generalization of that model where the adversary’s observation may be corrupted over a noisy discrete memoryless channel. Through the adversary’s myopicity, one can unify the slew of different adversary models, ranging from the omniscient adversary to one that is completely blind to the transmission (the latter is the well known oblivious model where the capacity is fully characterized).In this work, we present new results on the capacity under both the omniscient and myopic adversary models. We completely characterize the positive capacity threshold over general AVCs with omniscient adversaries. The characterization is in terms of two key combinatorial objects: the set of completely positive distributions and the CP-confusability set. For omniscient AVCs with positive capacity, we present non-trivial lower and upper bounds on the capacity; unlike some of the previous bounds, our bounds hold under fairly general input and jamming constraints. Our lower bound improves upon the generalized Gilbert-Varshamov bound for general AVCs while the upper bound generalizes the well known Elias-Bassalygo bound (known for binary and q-ary alphabets). For the myopic AVCs, we build on prior results known for the so-called sufficiently myopic model, and present new results on the positive rate communication threshold over the so-called insufficiently myopic regime (a completely insufficient myopic adversary specializes to an omniscient adversary). We present interesting examples for the widely studied models of adversarial bit-flip and bit-erasure channels. In fact, for the bit-flip AVC with additive adversarial noise as well as random noise, we completely characterize the omniscient model capacity when the random noise is sufficiently large vis-a-vis the adversary’s budget.
AU - Yadav, Anuj Kumar
AU - Alimohammadi, Mohammadreza
AU - Zhang, Yihan
AU - Budkuley, Amitalok J.
AU - Jaggi, Sidharth
ID - 12017
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - New results on AVCs with omniscient and myopic adversaries
VL - 2022
ER -
TY - JOUR
AB - A domain is called Kac regular for a quadratic form on L2 if every functions vanishing almost everywhere outside the domain can be approximated in form norm by functions with compact support in the domain. It is shown that this notion is stable under domination of quadratic forms. As applications measure perturbations of quasi-regular Dirichlet forms, Cheeger energies on metric measure spaces and Schrödinger operators on manifolds are studied. Along the way a characterization of the Sobolev space with Dirichlet boundary conditions on domains in infinitesimally Riemannian metric measure spaces is obtained.
AU - Wirth, Melchior
ID - 11916
IS - 3
JF - Advances in Operator Theory
KW - Algebra and Number Theory
KW - Analysis
TI - Kac regularity and domination of quadratic forms
VL - 7
ER -
TY - CONF
AB - We study the problem of characterizing the maximal rates of list decoding in Euclidean spaces for finite list sizes. For any positive integer L ≥ 2 and real N > 0, we say that a subset C⊂Rn is an (N,L – 1)-multiple packing or an (N,L– 1)-list decodable code if every Euclidean ball of radius nN−−−√ in ℝ n contains no more than L − 1 points of C. We study this problem with and without ℓ 2 norm constraints on C, and derive the best-known lower bounds on the maximal rate for (N,L−1) multiple packing. Our bounds are obtained via error exponents for list decoding over Additive White Gaussian Noise (AWGN) channels. We establish a curious inequality which relates the error exponent, a quantity of average-case nature, to the list-decoding radius, a quantity of worst-case nature. We derive various bounds on the error exponent for list decoding in both bounded and unbounded settings which could be of independent interest beyond multiple packing.
AU - Zhang, Yihan
AU - Vatedka, Shashank
ID - 12018
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - Lower bounds on list decoding capacity using error exponents
VL - 2022
ER -
TY - CONF
AB - This paper studies combinatorial properties of codes for the Z-channel. A Z-channel with error fraction τ takes as input a length-n binary codeword and injects in an adversarial manner up to nτ asymmetric errors, i.e., errors that only zero out bits but do not flip 0’s to 1’s. It is known that the largest (L − 1)-list-decodable code for the Z-channel with error fraction τ has exponential (in n) size if τ is less than a critical value that we call the Plotkin point and has constant size if τ is larger than the threshold. The (L−1)-list-decoding Plotkin point is known to be L−1L−1−L−LL−1. In this paper, we show that the largest (L−1)-list-decodable code ε-above the Plotkin point has size Θ L (ε −3/2 ) for any L − 1 ≥ 1.
AU - Polyanskii, Nikita
AU - Zhang, Yihan
ID - 12019
SN - 2157-8095
T2 - 2022 IEEE International Symposium on Information Theory
TI - List-decodable zero-rate codes for the Z-channel
VL - 2022
ER -
TY - JOUR
AB - Proximity-dependent protein labeling provides a powerful in vivo strategy to characterize the interactomes of specific proteins. We previously optimized a proximity labeling protocol for Caenorhabditis elegans using the highly active biotin ligase TurboID. A significant constraint on the sensitivity of TurboID is the presence of abundant endogenously biotinylated proteins that take up bandwidth in the mass spectrometer, notably carboxylases that use biotin as a cofactor. In C. elegans, these comprise POD-2/acetyl-CoA carboxylase alpha, PCCA-1/propionyl-CoA carboxylase alpha, PYC-1/pyruvate carboxylase, and MCCC-1/methylcrotonyl-CoA carboxylase alpha. Here, we developed ways to remove these carboxylases prior to streptavidin purification and mass spectrometry by engineering their corresponding genes to add a C-terminal His10 tag. This allows us to deplete them from C. elegans lysates using immobilized metal affinity chromatography. To demonstrate the method's efficacy, we use it to expand the interactome map of the presynaptic active zone protein ELKS-1. We identify many known active zone proteins, including UNC-10/RIM, SYD-2/liprin-alpha, SAD-1/BRSK1, CLA-1/CLArinet, C16E9.2/Sentryn, as well as previously uncharacterized potentially synaptic proteins such as the ortholog of human angiomotin, F59C12.3 and the uncharacterized protein R148.3. Our approach provides a quick and inexpensive solution to a common contaminant problem in biotin-dependent proximity labeling. The approach may be applicable to other model organisms and will enable deeper and more complete analysis of interactors for proteins of interest.
AU - Artan, Murat
AU - Hartl, Markus
AU - Chen, Weiqiang
AU - De Bono, Mario
ID - 12082
IS - 9
JF - Journal of Biological Chemistry
SN - 0021-9258
TI - Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans
VL - 298
ER -
TY - JOUR
AB - We extend the recent rigorous convergence result of Abels and Moser (SIAM J Math Anal 54(1):114–172, 2022. https://doi.org/10.1137/21M1424925) concerning convergence rates for solutions of the Allen–Cahn equation with a nonlinear Robin boundary condition towards evolution by mean curvature flow with constant contact angle. More precisely, in the present work we manage to remove the perturbative assumption on the contact angle being close to 90∘. We establish under usual double-well type assumptions on the potential and for a certain class of boundary energy densities the sub-optimal convergence rate of order ε12 for general contact angles α∈(0,π). For a very specific form of the boundary energy density, we even obtain from our methods a sharp convergence rate of order ε; again for general contact angles α∈(0,π). Our proof deviates from the popular strategy based on rigorous asymptotic expansions and stability estimates for the linearized Allen–Cahn operator. Instead, we follow the recent approach by Fischer et al. (SIAM J Math Anal 52(6):6222–6233, 2020. https://doi.org/10.1137/20M1322182), thus relying on a relative entropy technique. We develop a careful adaptation of their approach in order to encode the constant contact angle condition. In fact, we perform this task at the level of the notion of gradient flow calibrations. This concept was recently introduced in the context of weak-strong uniqueness for multiphase mean curvature flow by Fischer et al. (arXiv:2003.05478v2).
AU - Hensel, Sebastian
AU - Moser, Maximilian
ID - 12079
IS - 6
JF - Calculus of Variations and Partial Differential Equations
SN - 0944-2669
TI - Convergence rates for the Allen–Cahn equation with boundary contact energy: The non-perturbative regime
VL - 61
ER -
TY - JOUR
AB - Selection accumulates information in the genome—it guides stochastically evolving populations toward states (genotype frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback–Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright–Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation, and recombination. Finally, the cost of maintaining information depends on how it is encoded: Specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.
AU - Hledik, Michal
AU - Barton, Nicholas H
AU - Tkačik, Gašper
ID - 12081
IS - 36
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Accumulation and maintenance of information in evolution
VL - 119
ER -
TY - JOUR
AB - Endocytosis is a multistep process involving the sequential recruitment and action of numerous proteins. This process can be divided into two phases: an early phase, in which sites of endocytosis are formed, and a late phase in which clathrin-coated vesicles are formed and internalized into the cytosol, but how these phases link to each other remains unclear. In this study, we demonstrate that anchoring the yeast Eps15-like protein Pan1p to the peroxisome triggers most of the events occurring during the late phase at the peroxisome. At this ectopic location, Pan1p recruits most proteins that function in the late phases—including actin nucleation promoting factors—and then initiates actin polymerization. Pan1p also recruited Prk1 kinase and actin depolymerizing factors, thereby triggering disassembly immediately after actin assembly and inducing dissociation of endocytic proteins from the peroxisome. These observations suggest that Pan1p is a key regulator for initiating, processing, and completing the late phase of endocytosis.
AU - Enshoji, Mariko
AU - Miyano, Yoshiko
AU - Yoshida, Nao
AU - Nagano, Makoto
AU - Watanabe, Minami
AU - Kunihiro, Mayumi
AU - Siekhaus, Daria E
AU - Toshima, Junko Y.
AU - Toshima, Jiro
ID - 12080
IS - 10
JF - Journal of Cell Biology
SN - 0021-9525
TI - Eps15/Pan1p is a master regulator of the late stages of the endocytic pathway
VL - 221
ER -
TY - JOUR
AB - Molecular catch bonds are ubiquitous in biology and essential for processes like leucocyte extravasion1 and cellular mechanosensing2. Unlike normal (slip) bonds, catch bonds strengthen under tension. The current paradigm is that this feature provides ‘strength on demand3’, thus enabling cells to increase rigidity under stress1,4,5,6. However, catch bonds are often weaker than slip bonds because they have cryptic binding sites that are usually buried7,8. Here we show that catch bonds render reconstituted cytoskeletal actin networks stronger than slip bonds, even though the individual bonds are weaker. Simulations show that slip bonds remain trapped in stress-free areas, whereas weak binding allows catch bonds to mitigate crack initiation by moving to high-tension areas. This ‘dissociation on demand’ explains how cells combine mechanical strength with the adaptability required for shape change, and is relevant to diseases where catch bonding is compromised7,9, including focal segmental glomerulosclerosis10 caused by the α-actinin-4 mutant studied here. We surmise that catch bonds are the key to create life-like materials.
AU - Mulla, Yuval
AU - Avellaneda Sarrió, Mario
AU - Roland, Antoine
AU - Baldauf, Lucia
AU - Jung, Wonyeong
AU - Kim, Taeyoon
AU - Tans, Sander J.
AU - Koenderink, Gijsje H.
ID - 12085
IS - 9
JF - Nature Materials
SN - 1476-1122
TI - Weak catch bonds make strong networks
VL - 21
ER -
TY - JOUR
AB - Following up on the recent work on lower Ricci curvature bounds for quantum systems, we introduce two noncommutative versions of curvature-dimension bounds for symmetric quantum Markov semigroups over matrix algebras. Under suitable such curvature-dimension conditions, we prove a family of dimension-dependent functional inequalities, a version of the Bonnet–Myers theorem and concavity of entropy power in the noncommutative setting. We also provide examples satisfying certain curvature-dimension conditions, including Schur multipliers over matrix algebras, Herz–Schur multipliers over group algebras and generalized depolarizing semigroups.
AU - Wirth, Melchior
AU - Zhang, Haonan
ID - 12087
JF - Annales Henri Poincare
SN - 1424-0637
TI - Curvature-dimension conditions for symmetric quantum Markov semigroups
ER -
TY - CONF
AB - We present a quantum-enabled microwave-telecom interface with bidirectional conversion efficiencies up to 15% and added input noise quanta as low as 0.16. Moreover, we observe evidence for electro-optic laser cooling and vacuum amplification.
AU - Sahu, Rishabh
AU - Hease, William J
AU - Rueda Sanchez, Alfredo R
AU - Arnold, Georg M
AU - Qiu, Liu
AU - Fink, Johannes M
ID - 12088
SN - 9781557528209
T2 - Conference on Lasers and Electro-Optics
TI - Realizing a quantum-enabled interconnect between microwave and telecom light
ER -
TY - CONF
AB - Spatial games form a widely-studied class of games from biology and physics modeling the evolution of social behavior. Formally, such a game is defined by a square (d by d) payoff matrix M and an undirected graph G. Each vertex of G represents an individual, that initially follows some strategy i ∈ {1,2,…,d}. In each round of the game, every individual plays the matrix game with each of its neighbors: An individual following strategy i meeting a neighbor following strategy j receives a payoff equal to the entry (i,j) of M. Then, each individual updates its strategy to its neighbors' strategy with the highest sum of payoffs, and the next round starts. The basic computational problems consist of reachability between configurations and the average frequency of a strategy. For general spatial games and graphs, these problems are in PSPACE. In this paper, we examine restricted setting: the game is a prisoner’s dilemma; and G is a subgraph of grid. We prove that basic computational problems for spatial games with prisoner’s dilemma on a subgraph of a grid are PSPACE-hard.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Jecker, Ismael R
AU - Svoboda, Jakub
ID - 12101
SN - 1868-8969
T2 - 42nd IARCS Annual Conference on Foundations of Software Technology and Theoretical Computer Science
TI - Complexity of spatial games
VL - 250
ER -
TY - JOUR
AB - A recently proposed approach for avoiding the ultraviolet divergence of Hamiltonians with particle creation is based on interior-boundary conditions (IBCs). The approach works well in the non-relativistic case, i.e., for the Laplacian operator. Here, we study how the approach can be applied to Dirac operators. While this has successfully been done already in one space dimension, and more generally for codimension-1 boundaries, the situation of point sources in three dimensions corresponds to a codimension-3 boundary. One would expect that, for such a boundary, Dirac operators do not allow for boundary conditions because they are known not to allow for point interactions in 3D, which also correspond to a boundary condition. Indeed, we confirm this expectation here by proving that there is no self-adjoint operator on a (truncated) Fock space that would correspond to a Dirac operator with an IBC at configurations with a particle at the origin. However, we also present a positive result showing that there are self-adjoint operators with an IBC (on the boundary consisting of configurations with a particle at the origin) that are away from those configurations, given by a Dirac operator plus a sufficiently strong Coulomb potential.
AU - Henheik, Sven Joscha
AU - Tumulka, Roderich
ID - 12110
IS - 12
JF - Journal of Mathematical Physics
SN - 0022-2488
TI - Interior-boundary conditions for the Dirac equation at point sources in three dimensions
VL - 63
ER -
TY - JOUR
AB - The sensitivity of coarse-grained daily extreme precipitation to sea surface temperature is analyzed using satellite precipitation estimates over the 300–302.5 K range. A theoretical scaling is proposed, linking changes in coarse-grained precipitation to changes in fine-scale hourly precipitation area fraction and changes in conditional fine-scale precipitation rates. The analysis reveals that the extreme coarse-grained precipitation scaling with temperature (∼7%/K) is dominated by the fine-scale precipitating fraction scaling (∼6.5%/K) when using a 3 mm/h fine-scale threshold to delineate the precipitating fraction. These results are shown to be robust to the selection of the precipitation product and to the percentile used to characterize the extreme. This new coarse-grained scaling is further related to the well-known scaling for fine-scale precipitation extremes, and suggests a compensation between thermodynamic and dynamic contributions or that both contributions are small with respect to that of fractional coverage. These results suggest that processes responsible for the changes in fractional coverage are to be accounted for to assess the sensitivity of coarse-grained extreme daily precipitation to surface temperature.
AU - Roca, Rémy
AU - De Meyer, Victorien
AU - Muller, Caroline J
ID - 12107
IS - 24
JF - Geophysical Research Letters
SN - 0094-8276
TI - Precipitating fraction, not intensity, explains extreme coarse-grained precipitation Clausius-Clapeyron scaling with sea surface temperature over tropical oceans
VL - 49
ER -
TY - JOUR
AB - Kelvin probe force microscopy (KPFM) is a powerful tool for studying contact electrification (CE) at the nanoscale, but converting KPFM voltage maps to charge density maps is nontrivial due to long-range forces and complex system geometry. Here we present a strategy using finite-element method (FEM) simulations to determine the Green's function of the KPFM probe/insulator/ground system, which allows us to quantitatively extract surface charge. Testing our approach with synthetic data, we find that accounting for the atomic force microscope (AFM) tip, cone, and cantilever is necessary to recover a known input and that existing methods lead to gross miscalculation or even the incorrect sign of the underlying charge. Applying it to experimental data, we demonstrate its capacity to extract realistic surface charge densities and fine details from contact-charged surfaces. Our method gives a straightforward recipe to convert qualitative KPFM voltage data into quantitative charge data over a range of experimental conditions, enabling quantitative CE at the nanoscale.
AU - Pertl, Felix
AU - Sobarzo Ponce, Juan Carlos A
AU - Shafeek, Lubuna B
AU - Cramer, Tobias
AU - Waitukaitis, Scott R
ID - 12109
IS - 12
JF - Physical Review Materials
TI - Quantifying nanoscale charge density features of contact-charged surfaces with an FEM/KPFM-hybrid approach
VL - 6
ER -
TY - JOUR
AB - Quantum impurities exhibit fascinating many-body phenomena when the small interacting impurity changes the physics of a large noninteracting environment. The characterisation of such strongly correlated nonperturbative effects is particularly challenging due to the infinite size of the environment, and the inability of local correlators to capture the buildup of long-ranged entanglement in the system. Here, we harness an entanglement-based observable—the purity of the impurity—as a witness for the formation of strong correlations. We showcase the utility of our scheme by exactly solving the open Kondo box model in the small box limit, and thus describe all-electronic dot-cavity devices. Specifically, we conclusively characterize the metal-to-insulator phase transition in the system and identify how the (conducting) dot-lead Kondo singlet is quenched by an (insulating) intraimpurity singlet formation. Furthermore, we propose an experimentally feasible tomography protocol for the measurement of the purity, which motivates the observation of impurity physics through their entanglement build up.
AU - Stocker, Lidia
AU - Sack, Stefan
AU - Ferguson, Michael S.
AU - Zilberberg, Oded
ID - 12111
IS - 4
JF - Physical Review Research
SN - 2643-1564
TI - Entanglement-based observables for quantum impurities
VL - 4
ER -
TY - JOUR
AB - The sequential exchange of filament composition to increase filament curvature was proposed as a mechanism for how some biological polymers deform and cut membranes. The relationship between the filament composition and its mechanical effect is lacking. We develop a kinetic model for the assembly of composite filaments that includes protein–membrane adhesion, filament mechanics and membrane mechanics. We identify the physical conditions for such a membrane remodeling and show this mechanism of sequential polymer assembly lowers the energetic barrier for membrane deformation.
AU - Meadowcroft, Billie
AU - Palaia, Ivan
AU - Pfitzner, Anna Katharina
AU - Roux, Aurélien
AU - Baum, Buzz
AU - Šarić, Anđela
ID - 12108
IS - 26
JF - Physical Review Letters
SN - 0031-9007
TI - Mechanochemical rules for shape-shifting filaments that remodel membranes
VL - 129
ER -
TY - JOUR
AB - The power factor of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) film can be significantly improved by optimizing the oxidation level of the film in oxidation and reduction processes. However, precise control over the oxidation and reduction effects in PEDOT:PSS remains a challenge, which greatly sacrifices both S and σ. Here, we propose a two-step post-treatment using a mixture of ethylene glycol (EG) and Arginine (Arg) and sulfuric acid (H2SO4) in sequence to engineer high-performance PEDOT:PSS thermoelectric films. The high-polarity EG dopant removes the excess non-ionized PSS and induces benzenoid-to-quinoid conformational change in the PEDOT:PSS films. In particular, basic amino acid Arg tunes the oxidation level of PEDOT:PSS and prevents the films from over-oxidation during H2SO4 post-treatment, leading to increased S. The following H2SO4 post-treatment further induces highly orientated lamellar stacking microstructures to increase σ, yielding a maximum power factor of 170.6 μW m−1 K−2 at 460 K. Moreover, a novel trigonal-shape thermoelectric device is designed and assembled by the as-prepared PEDOT:PSS films in order to harvest heat via a vertical temperature gradient. An output power density of 33 μW cm−2 is generated at a temperature difference of 40 K, showing the potential application for low-grade wearable electronic devices.
AU - Zhang, Li
AU - Liu, Xingyu
AU - Wu, Ting
AU - Xu, Shengduo
AU - Suo, Guoquan
AU - Ye, Xiaohui
AU - Hou, Xiaojiang
AU - Yang, Yanling
AU - Liu, Qingfeng
AU - Wang, Hongqiang
ID - 12113
JF - Applied Surface Science
KW - Surfaces
KW - Coatings and Films
KW - Condensed Matter Physics
KW - Surfaces and Interfaces
KW - General Physics and Astronomy
KW - General Chemistry
SN - 0169-4332
TI - Two-step post-treatment to deliver high performance thermoelectric device with vertical temperature gradient
VL - 613
ER -
TY - JOUR
AB - Russia’s unprovoked attack on Ukraine has destroyed civilian infrastructure, including universities, research centers, and other academic infrastructure (1). Many Ukrainian scholars and researchers remain in Ukraine, and their work has suffered from major setbacks (2–4). We call on international scientists and institutions to support them.
AU - Chhugani, Karishma
AU - Frolova, Alina
AU - Salyha, Yuriy
AU - Fiscutean, Andrada
AU - Zlenko, Oksana
AU - Reinsone, Sanita
AU - Wolfsberger, Walter W.
AU - Ivashchenko, Oleksandra V.
AU - Maci, Megi
AU - Dziuba, Dmytro
AU - Parkhomenko, Andrii
AU - Bortz, Eric
AU - Kondrashov, Fyodor
AU - Łabaj, Paweł P.
AU - Romero, Veronika
AU - Hlávka, Jakub
AU - Oleksyk, Taras K.
AU - Mangul, Serghei
ID - 12116
IS - 6626
JF - Science
SN - 0036-8075
TI - Remote opportunities for scholars in Ukraine
VL - 378
ER -
TY - JOUR
AB - Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain.
AU - Bartalska, Katarina
AU - Hübschmann, Verena
AU - Korkut, Medina
AU - Cubero, Ryan J
AU - Venturino, Alessandro
AU - Rössler, Karl
AU - Czech, Thomas
AU - Siegert, Sandra
ID - 11478
IS - 7
JF - iScience
TI - A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation
VL - 25
ER -
TY - JOUR
AB - To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.
For complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1
AU - Hübschmann, Verena
AU - Korkut, Medina
AU - Siegert, Sandra
ID - 12117
IS - 4
JF - STAR Protocols
KW - General Immunology and Microbiology
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Neuroscience
SN - 2666-1667
TI - Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay
VL - 3
ER -
TY - JOUR
AB - Activity of sensory neurons is driven not only by external stimuli but also by feedback signals from higher brain areas. Attention is one particularly important internal signal whose presumed role is to modulate sensory representations such that they only encode information currently relevant to the organism at minimal cost. This hypothesis has, however, not yet been expressed in a normative computational framework. Here, by building on normative principles of probabilistic inference and efficient coding, we developed a model of dynamic population coding in the visual cortex. By continuously adapting the sensory code to changing demands of the perceptual observer, an attention-like modulation emerges. This modulation can dramatically reduce the amount of neural activity without deteriorating the accuracy of task-specific inferences. Our results suggest that a range of seemingly disparate cortical phenomena such as intrinsic gain modulation, attention-related tuning modulation, and response variability could be manifestations of the same underlying principles, which combine efficient sensory coding with optimal probabilistic inference in dynamic environments.
AU - Mlynarski, Wiktor F
AU - Tkačik, Gašper
ID - 12332
IS - 12
JF - PLoS Biology
TI - Efficient coding theory of dynamic attentional modulation
VL - 20
ER -
TY - JOUR
AB - Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.
AU - Petzold, Tobias
AU - Zhang, Zhe
AU - Ballesteros, Iván
AU - Saleh, Inas
AU - Polzin, Amin
AU - Thienel, Manuela
AU - Liu, Lulu
AU - Ul Ain, Qurrat
AU - Ehreiser, Vincent
AU - Weber, Christian
AU - Kilani, Badr
AU - Mertsch, Pontus
AU - Götschke, Jeremias
AU - Cremer, Sophie
AU - Fu, Wenwen
AU - Lorenz, Michael
AU - Ishikawa-Ankerhold, Hellen
AU - Raatz, Elisabeth
AU - El-Nemr, Shaza
AU - Görlach, Agnes
AU - Marhuenda, Esther
AU - Stark, Konstantin
AU - Pircher, Joachim
AU - Stegner, David
AU - Gieger, Christian
AU - Schmidt-Supprian, Marc
AU - Gärtner, Florian R
AU - Almendros, Isaac
AU - Kelm, Malte
AU - Schulz, Christian
AU - Hidalgo, Andrés
AU - Massberg, Steffen
ID - 12119
IS - 12
JF - Immunity
KW - Infectious Diseases
KW - Immunology
KW - Immunology and Allergy
SN - 1074-7613
TI - Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease
VL - 55
ER -
TY - JOUR
AB - Autophagosomes are double-membraned vesicles that traffic harmful or unwanted cellular macromolecules to the vacuole for recycling. Although autophagosome biogenesis has been extensively studied, autophagosome maturation, i.e., delivery and fusion with the vacuole, remains largely unknown in plants. Here, we have identified an autophagy adaptor, CFS1, that directly interacts with the autophagosome marker ATG8 and localizes on both membranes of the autophagosome. Autophagosomes form normally in Arabidopsis thaliana cfs1 mutants, but their delivery to the vacuole is disrupted. CFS1’s function is evolutionarily conserved in plants, as it also localizes to the autophagosomes and plays a role in autophagic flux in the liverwort Marchantia polymorpha. CFS1 regulates autophagic flux by bridging autophagosomes with the multivesicular body-localized ESCRT-I component VPS23A, leading to the formation of amphisomes. Similar to CFS1-ATG8 interaction, disrupting the CFS1-VPS23A interaction blocks autophagic flux and renders plants sensitive to nitrogen starvation. Altogether, our results reveal a conserved vacuolar sorting hub that regulates autophagic flux in plants.
AU - Zhao, Jierui
AU - Bui, Mai Thu
AU - Ma, Juncai
AU - Künzl, Fabian
AU - Picchianti, Lorenzo
AU - De La Concepcion, Juan Carlos
AU - Chen, Yixuan
AU - Petsangouraki, Sofia
AU - Mohseni, Azadeh
AU - García-Leon, Marta
AU - Gomez, Marta Salas
AU - Giannini, Caterina
AU - Gwennogan, Dubois
AU - Kobylinska, Roksolana
AU - Clavel, Marion
AU - Schellmann, Swen
AU - Jaillais, Yvon
AU - Friml, Jiří
AU - Kang, Byung-Ho
AU - Dagdas, Yasin
ID - 12121
IS - 12
JF - Journal of Cell Biology
KW - Cell Biology
SN - 0021-9525
TI - Plant autophagosomes mature into amphisomes prior to their delivery to the central vacuole
VL - 221
ER -
TY - JOUR
AB - We introduce a machine-learning (ML) framework for high-throughput benchmarking of diverse representations of chemical systems against datasets of materials and molecules. The guiding principle underlying the benchmarking approach is to evaluate raw descriptor performance by limiting model complexity to simple regression schemes while enforcing best ML practices, allowing for unbiased hyperparameter optimization, and assessing learning progress through learning curves along series of synchronized train-test splits. The resulting models are intended as baselines that can inform future method development, in addition to indicating how easily a given dataset can be learnt. Through a comparative analysis of the training outcome across a diverse set of physicochemical, topological and geometric representations, we glean insight into the relative merits of these representations as well as their interrelatedness.
AU - Poelking, Carl
AU - Faber, Felix A
AU - Cheng, Bingqing
ID - 12128
IS - 4
JF - Machine Learning: Science and Technology
KW - Artificial Intelligence
KW - Human-Computer Interaction
KW - Software
SN - 2632-2153
TI - BenchML: An extensible pipelining framework for benchmarking representations of materials and molecules at scale
VL - 3
ER -
TY - JOUR
AB - Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.
AU - Tomanek, Isabella
AU - Guet, Calin C
ID - 12333
JF - eLife
TI - Adaptation dynamics between copynumber and point mutations
VL - 11
ER -
TY - JOUR
AB - Centrosomes play a crucial role during immune cell interactions and initiation of the immune response. In proliferating cells, centrosome numbers are tightly controlled and generally limited to one in G1 and two prior to mitosis. Defects in regulating centrosome numbers have been associated with cell transformation and tumorigenesis. Here, we report the emergence of extra centrosomes in leukocytes during immune activation. Upon antigen encounter, dendritic cells pass through incomplete mitosis and arrest in the subsequent G1 phase leading to tetraploid cells with accumulated centrosomes. In addition, cell stimulation increases expression of polo-like kinase 2, resulting in diploid cells with two centrosomes in G1-arrested cells. During cell migration, centrosomes tightly cluster and act as functional microtubule-organizing centers allowing for increased persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with extra centrosomes display enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of extra centrosomes for regular cell and tissue homeostasis.
AU - Weier, Ann-Kathrin
AU - Homrich, Mirka
AU - Ebbinghaus, Stephanie
AU - Juda, Pavel
AU - Miková, Eliška
AU - Hauschild, Robert
AU - Zhang, Lili
AU - Quast, Thomas
AU - Mass, Elvira
AU - Schlitzer, Andreas
AU - Kolanus, Waldemar
AU - Burgdorf, Sven
AU - Gruß, Oliver J.
AU - Hons, Miroslav
AU - Wieser, Stefan
AU - Kiermaier, Eva
ID - 12122
IS - 12
JF - Journal of Cell Biology
KW - Cell Biology
SN - 0021-9525
TI - Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells
VL - 221
ER -
TY - JOUR
AB - Plant root architecture flexibly adapts to changing nitrate (NO3−) availability in the soil; however, the underlying molecular mechanism of this adaptive development remains under-studied. To explore the regulation of NO3−-mediated root growth, we screened for low-nitrate-resistant mutant (lonr) and identified mutants that were defective in the NAC transcription factor NAC075 (lonr1) as being less sensitive to low NO3− in terms of primary root growth. We show that NAC075 is a mobile transcription factor relocating from the root stele tissues to the endodermis based on NO3− availability. Under low-NO3− availability, the kinase CBL-interacting protein kinase 1 (CIPK1) is activated, and it phosphorylates NAC075, restricting its movement from the stele, which leads to the transcriptional regulation of downstream target WRKY53, consequently leading to adapted root architecture. Our work thus identifies an adaptive mechanism involving translocation of transcription factor based on nutrient availability and leading to cell-specific reprogramming of plant root growth.
AU - Xiao, Huixin
AU - Hu, Yumei
AU - Wang, Yaping
AU - Cheng, Jinkui
AU - Wang, Jinyi
AU - Chen, Guojingwei
AU - Li, Qian
AU - Wang, Shuwei
AU - Wang, Yalu
AU - Wang, Shao-Shuai
AU - Wang, Yi
AU - Xuan, Wei
AU - Li, Zhen
AU - Guo, Yan
AU - Gong, Zhizhong
AU - Friml, Jiří
AU - Zhang, Jing
ID - 12120
IS - 23
JF - Developmental Cell
KW - Developmental Biology
KW - Cell Biology
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - Molecular Biology
SN - 1534-5807
TI - Nitrate availability controls translocation of the transcription factor NAC075 for cell-type-specific reprogramming of root growth
VL - 57
ER -
TY - GEN
AB - Copy-number and point mutations form the basis for most evolutionary novelty through the process of gene duplication and divergence. While a plethora of genomic sequence data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic system that allows us to distinguish copy-number and point mutations, we study their early and transient adaptive dynamics in real-time in Escherichia coli. We find two qualitatively different routes of adaptation depending on the level of functional improvement selected for: In conditions of high gene expression demand, the two types of mutations occur as a combination. Under low gene expression demand, negative epistasis between the two types of mutations renders them mutually exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation but also constrain sequence divergence over evolutionary time scales.
AU - Tomanek, Isabella
AU - Guet, Calin C
ID - 12339
TI - Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose
ER -
TY - JOUR
AB - Given a finite point set P in general position in the plane, a full triangulation of P is a maximal straight-line embedded plane graph on P. A partial triangulation of P is a full triangulation of some subset P′ of P containing all extreme points in P. A bistellar flip on a partial triangulation either flips an edge (called edge flip), removes a non-extreme point of degree 3, or adds a point in P∖P′ as vertex of degree 3. The bistellar flip graph has all partial triangulations as vertices, and a pair of partial triangulations is adjacent if they can be obtained from one another by a bistellar flip. The edge flip graph is defined with full triangulations as vertices, and edge flips determining the adjacencies. Lawson showed in the early seventies that these graphs are connected. The goal of this paper is to investigate the structure of these graphs, with emphasis on their vertex connectivity. For sets P of n points in the plane in general position, we show that the edge flip graph is ⌈n/2−2⌉-vertex connected, and the bistellar flip graph is (n−3)-vertex connected; both results are tight. The latter bound matches the situation for the subfamily of regular triangulations (i.e., partial triangulations obtained by lifting the points to 3-space and projecting back the lower convex hull), where (n−3)-vertex connectivity has been known since the late eighties through the secondary polytope due to Gelfand, Kapranov, & Zelevinsky and Balinski’s Theorem. For the edge flip-graph, we additionally show that the vertex connectivity is at least as large as (and hence equal to) the minimum degree (i.e., the minimum number of flippable edges in any full triangulation), provided that n is large enough. Our methods also yield several other results: (i) The edge flip graph can be covered by graphs of polytopes of dimension ⌈n/2−2⌉ (products of associahedra) and the bistellar flip graph can be covered by graphs of polytopes of dimension n−3 (products of secondary polytopes). (ii) A partial triangulation is regular, if it has distance n−3 in the Hasse diagram of the partial order of partial subdivisions from the trivial subdivision. (iii) All partial triangulations of a point set are regular iff the partial order of partial subdivisions has height n−3. (iv) There are arbitrarily large sets P with non-regular partial triangulations and such that every proper subset has only regular triangulations, i.e., there are no small certificates for the existence of non-regular triangulations.
AU - Wagner, Uli
AU - Welzl, Emo
ID - 12129
IS - 4
JF - Discrete & Computational Geometry
KW - Computational Theory and Mathematics
KW - Discrete Mathematics and Combinatorics
KW - Geometry and Topology
KW - Theoretical Computer Science
SN - 0179-5376
TI - Connectivity of triangulation flip graphs in the plane
VL - 68
ER -
TY - JOUR
AB - Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines.
AU - Byazrova, Maria G.
AU - Astakhova, Ekaterina A.
AU - Minnegalieva, Aygul
AU - Sukhova, Maria M.
AU - Mikhailov, Artem A.
AU - Prilipov, Alexey G.
AU - Gorchakov, Andrey A.
AU - Filatov, Alexander V.
ID - 12131
JF - npj Vaccines
KW - Pharmacology (medical)
KW - Infectious Diseases
KW - Pharmacology
KW - Immunology
KW - SARS-COV-2
KW - COVID
SN - 2059-0105
TI - Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination
VL - 7
ER -
TY - JOUR
AB - Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.
AU - Huang, Jian
AU - Zhao, Lei
AU - Malik, Shikha
AU - Gentile, Benjamin R.
AU - Xiong, Va
AU - Arazi, Tzahi
AU - Owen, Heather A.
AU - Friml, Jiří
AU - Zhao, Dazhong
ID - 12130
JF - Nature Communications
KW - General Physics and Astronomy
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Chemistry
KW - Multidisciplinary
SN - 2041-1723
TI - Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis
VL - 13
ER -
TY - JOUR
AB - MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucleases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is specifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer’s DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the complete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicer⋅miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleavage-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways.
AU - Zapletal, David
AU - Taborska, Eliska
AU - Pasulka, Josef
AU - Malik, Radek
AU - Kubicek, Karel
AU - Zanova, Martina
AU - Much, Christian
AU - Sebesta, Marek
AU - Buccheri, Valeria
AU - Horvat, Filip
AU - Jenickova, Irena
AU - Prochazkova, Michaela
AU - Prochazka, Jan
AU - Pinkas, Matyas
AU - Novacek, Jiri
AU - Joseph, Diego F.
AU - Sedlacek, Radislav
AU - Bernecky, Carrie A
AU - O’Carroll, Dónal
AU - Stefl, Richard
AU - Svoboda, Petr
ID - 12143
IS - 21
JF - Molecular Cell
KW - Cell Biology
KW - Molecular Biology
SN - 1097-2765
TI - Structural and functional basis of mammalian microRNA biogenesis by Dicer
VL - 82
ER -