@article{10862,
  abstract     = {We consider the sum of two large Hermitian matrices A and B with a Haar unitary conjugation bringing them into a general relative position. We prove that the eigenvalue density on the scale slightly above the local eigenvalue spacing is asymptotically given by the free additive convolution of the laws of A and B as the dimension of the matrix increases. This implies optimal rigidity of the eigenvalues and optimal rate of convergence in Voiculescu's theorem. Our previous works [4], [5] established these results in the bulk spectrum, the current paper completely settles the problem at the spectral edges provided they have the typical square-root behavior. The key element of our proof is to compensate the deterioration of the stability of the subordination equations by sharp error estimates that properly account for the local density near the edge. Our results also hold if the Haar unitary matrix is replaced by the Haar orthogonal matrix.},
  author       = {Bao, Zhigang and Erdös, László and Schnelli, Kevin},
  issn         = {0022-1236},
  journal      = {Journal of Functional Analysis},
  keywords     = {Analysis},
  number       = {7},
  publisher    = {Elsevier},
  title        = {{Spectral rigidity for addition of random matrices at the regular edge}},
  doi          = {10.1016/j.jfa.2020.108639},
  volume       = {279},
  year         = {2020},
}

@inbook{10865,
  abstract     = {We introduce the notion of Witness Maps as a cryptographic notion of a proof system. A Unique Witness Map (UWM) deterministically maps all witnesses for an   NP  statement to a single representative witness, resulting in a computationally sound, deterministic-prover, non-interactive witness independent proof system. A relaxation of UWM, called Compact Witness Map (CWM), maps all the witnesses to a small number of witnesses, resulting in a “lossy” deterministic-prover, non-interactive proof-system. We also define a Dual Mode Witness Map (DMWM) which adds an “extractable” mode to a CWM.
Our main construction is a DMWM for all   NP  relations, assuming sub-exponentially secure indistinguishability obfuscation (  iO ), along with standard cryptographic assumptions. The DMWM construction relies on a CWM and a new primitive called Cumulative All-Lossy-But-One Trapdoor Functions (C-ALBO-TDF), both of which are in turn instantiated based on   iO  and other primitives. Our instantiation of a CWM is in fact a UWM; in turn, we show that a UWM implies Witness Encryption. Along the way to constructing UWM and C-ALBO-TDF, we also construct, from standard assumptions, Puncturable Digital Signatures and a new primitive called Cumulative Lossy Trapdoor Functions (C-LTDF). The former improves up on a construction of Bellare et al. (Eurocrypt 2016), who relied on sub-exponentially secure   iO  and sub-exponentially secure OWF.
As an application of our constructions, we show how to use a DMWM to construct the first leakage and tamper-resilient signatures with a deterministic signer, thereby solving a decade old open problem posed by Katz and Vaikunthanathan (Asiacrypt 2009), by Boyle, Segev and Wichs (Eurocrypt 2011), as well as by Faonio and Venturi (Asiacrypt 2016). Our construction achieves the optimal leakage rate of   1−o(1) .},
  author       = {Chakraborty, Suvradip and Prabhakaran, Manoj and Wichs, Daniel},
  booktitle    = {Public-Key Cryptography},
  editor       = {Kiayias, A},
  isbn         = {9783030453732},
  issn         = {1611-3349},
  pages        = {220--246},
  publisher    = {Springer Nature},
  title        = {{Witness maps and applications}},
  doi          = {10.1007/978-3-030-45374-9_8},
  volume       = {12110},
  year         = {2020},
}

@article{10866,
  abstract     = {Recent discoveries have shown that, when two layers of van der Waals (vdW) materials are superimposed with a relative twist angle between them, the electronic properties of the coupled system can be dramatically altered. Here, we demonstrate that a similar concept can be extended to the optics realm, particularly to propagating phonon polaritons–hybrid light-matter interactions. To do this, we fabricate stacks composed of two twisted slabs of a vdW crystal (α-MoO3) supporting anisotropic phonon polaritons (PhPs), and image the propagation of the latter when launched by localized sources. Our images reveal that, under a critical angle, the PhPs isofrequency curve undergoes a topological transition, in which the propagation of PhPs is strongly guided (canalization regime) along predetermined directions without geometric spreading. These results demonstrate a new degree of freedom (twist angle) for controlling the propagation of polaritons at the nanoscale with potential for nanoimaging, (bio)-sensing, or heat management.},
  author       = {Duan, Jiahua and Capote-Robayna, Nathaniel and Taboada-Gutiérrez, Javier and Álvarez-Pérez, Gonzalo and Prieto Gonzalez, Ivan and Martín-Sánchez, Javier and Nikitin, Alexey Y. and Alonso-González, Pablo},
  issn         = {1530-6992},
  journal      = {Nano Letters},
  keywords     = {Mechanical Engineering, Condensed Matter Physics, General Materials Science, General Chemistry, Bioengineering},
  number       = {7},
  pages        = {5323--5329},
  publisher    = {American Chemical Society},
  title        = {{Twisted nano-optics: Manipulating light at the nanoscale with twisted phonon polaritonic slabs}},
  doi          = {10.1021/acs.nanolett.0c01673},
  volume       = {20},
  year         = {2020},
}

@article{10867,
  abstract     = {In this paper we find a tight estimate for Gromov’s waist of the balls in spaces of constant curvature, deduce the estimates for the balls in Riemannian manifolds with upper bounds on the curvature (CAT(ϰ)-spaces), and establish similar result for normed spaces.},
  author       = {Akopyan, Arseniy and Karasev, Roman},
  issn         = {1687-0247},
  journal      = {International Mathematics Research Notices},
  keywords     = {General Mathematics},
  number       = {3},
  pages        = {669--697},
  publisher    = {Oxford University Press},
  title        = {{Waist of balls in hyperbolic and spherical spaces}},
  doi          = {10.1093/imrn/rny037},
  volume       = {2020},
  year         = {2020},
}

@inproceedings{12901,
  author       = {Schlögl, Alois and Kiss, Janos and Elefante, Stefano},
  booktitle    = {AHPC19 - Austrian HPC Meeting 2019 },
  location     = {Grundlsee, Austria},
  pages        = {25},
  publisher    = {Institut für Mathematik und wissenschaftliches Rechnen der Universität Graz},
  title        = {{Is Debian suitable for running an HPC Cluster?}},
  year         = {2019},
}

@misc{13067,
  abstract     = {Genetic incompatibilities contribute to reproductive isolation between many diverging populations, but it is still unclear to what extent they play a role if divergence happens with gene flow. In contact zones between the "Crab" and "Wave" ecotypes of the snail Littorina saxatilis divergent selection forms strong barriers to gene flow, while the role of postzygotic barriers due to selection against hybrids remains unclear. High embryo abortion rates in this species could indicate the presence of such barriers. Postzygotic barriers might include genetic incompatibilities (e.g. Dobzhansky-Muller incompatibilities) but also maladaptation, both expected to be most pronounced in contact zones. In addition, embryo abortion might reflect physiological stress on females and embryos independent of any genetic stress. We examined all embryos of &gt;500 females sampled outside and inside contact zones of three populations in Sweden. Females' clutch size ranged from 0 to 1011 embryos (mean 130±123) and abortion rates varied between 0 and100% (mean 12%). We described female genotypes by using a hybrid index based on hundreds of SNPs differentiated between ecotypes with which we characterised female genotypes. We also calculated female SNP heterozygosity and inversion karyotype. Clutch size did not vary with female hybrid index and abortion rates were only weakly related to hybrid index in two sites but not at all in a third site. No additional variation in abortion rate was explained by female SNP heterozygosity, but increased female inversion heterozygosity added slightly to increased abortion. Our results show only weak and probably biologically insignificant postzygotic barriers contributing to ecotype divergence and the high and variable abortion rates were marginally, if at all, explained by hybrid index of females.},
  author       = {Johannesson, Kerstin and Zagrodzka, Zuzanna and Faria, Rui and Westram, Anja M and Butlin, Roger},
  publisher    = {Dryad},
  title        = {{Data from: Is embryo abortion a postzygotic barrier to gene flow between Littorina ecotypes?}},
  doi          = {10.5061/DRYAD.TB2RBNZWK},
  year         = {2019},
}

@inbook{8281,
  abstract     = {We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it.},
  author       = {Barton, Nicholas H and Etheridge, Alison},
  booktitle    = {Handbook of statistical genomics},
  editor       = {Balding, David and Moltke, Ida and Marioni, John},
  isbn         = {9781119429142},
  pages        = {115--144},
  publisher    = {Wiley},
  title        = {{Mathematical models in population genetics}},
  doi          = {10.1002/9781119487845.ch4},
  year         = {2019},
}

@unpublished{8305,
  abstract     = {In this paper, we present the first fully asynchronous distributed key generation (ADKG) algorithm as well as the first distributed key generation algorithm that can create keys with a dual (f,2f+1)−threshold that are necessary for scalable consensus (which so far needs a trusted dealer assumption). In order to create a DKG with a dual (f,2f+1)− threshold we first answer in the affirmative the open question posed by Cachin et al. how to create an AVSS protocol with recovery thresholds f+1<k≤2f+1, which is of independent interest. Our High-threshold-AVSS (HAVSS) uses an asymmetric bi-variate polynomial, where the secret shared is hidden from any set of k nodes but an honest node that did not participate in the sharing phase can still recover his share with only n−2f shares, hence be able to contribute in the secret reconstruction. Another building block for ADKG is a novel Eventually Perfect Common Coin (EPCC) abstraction and protocol that enables the participants to create a common coin that might fail to agree at most f+1 times (even if invoked a polynomial number of times). Using EPCC we implement an Eventually Efficient Asynchronous Binary Agreement (EEABA) in which each instance takes O(n2) bits and O(1) rounds in expectation, except for at most f+1 instances which may take O(n4) bits and O(n) rounds in total. Using EEABA we construct the first fully Asynchronous Distributed Key Generation (ADKG) which has the same overhead and expected runtime as the best partially-synchronous DKG (O(n4) words, O(n) rounds). As a corollary of our ADKG we can also create the first Validated Asynchronous Byzantine Agreement (VABA) in the authenticated setting that does not need a trusted dealer to setup threshold signatures of degree n−f. Our VABA has an overhead of expected O(n2) words and O(1) time per instance after an initial O(n4) words and O(n) time bootstrap via ADKG.},
  author       = {KOKORIS KOGIAS, Eleftherios and Spiegelman, Alexander and Malkhi, Dahlia and Abraham, Ittai},
  booktitle    = {Cryptology ePrint Archive},
  title        = {{Bootstrapping consensus without trusted setup: fully asynchronous distributed key generation}},
  year         = {2019},
}

@inproceedings{8570,
  abstract     = {This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with linear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In its third edition, seven tools have been applied to solve six different benchmark problems in the category for linear continuous dynamics (in alphabetical order): CORA, CORA/SX, HyDRA, Hylaa, JuliaReach, SpaceEx, and XSpeed. This report is a snapshot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results provide one of the most complete assessments of tools for the safety verification of continuous and hybrid systems with linear continuous dynamics up to this date.</jats:p>},
  author       = {Althoff, Matthias and Bak, Stanley and Forets, Marcelo and Frehse, Goran and Kochdumper, Niklas and Ray, Rajarshi and Schilling, Christian and Schupp, Stefan},
  booktitle    = {EPiC Series in Computing},
  issn         = {23987340},
  location     = {Montreal, Canada},
  pages        = {14--40},
  publisher    = {EasyChair},
  title        = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with linear continuous dynamics}},
  doi          = {10.29007/bj1w},
  volume       = {61},
  year         = {2019},
}

@inproceedings{9261,
  abstract     = {Bending-active structures are able to efficiently produce complex curved shapes starting from flat panels. The desired deformation of the panels derives from the proper selection of their elastic properties. Optimized panels, called FlexMaps, are designed such that, once they are bent and assembled, the resulting static equilibrium configuration matches a desired input 3D shape. The FlexMaps elastic properties are controlled by locally varying spiraling geometric mesostructures, which are optimized in size and shape to match the global curvature (i.e., bending requests) of the target shape. The design pipeline starts from a quad mesh representing the input 3D shape, which defines the edge size and the total amount of spirals: every quad will embed one spiral. Then, an optimization algorithm tunes the geometry of the spirals by using a simplified pre-computed rod model. This rod model is derived from a non-linear regression algorithm which approximates the non-linear behavior of solid FEM spiral models subject to hundreds of load combinations. This innovative pipeline has been applied to the project of a lightweight plywood pavilion named FlexMaps Pavilion, which is a single-layer piecewise twisted arc that fits a bounding box of 3.90x3.96x3.25 meters.},
  author       = {Laccone, Francesco and Malomo, Luigi and Perez Rodriguez, Jesus and Pietroni, Nico and Ponchio, Federico and Bickel, Bernd and Cignoni, Paolo},
  booktitle    = {IASS Symposium 2019 - 60th Anniversary Symposium of the International Association for Shell and Spatial Structures; Structural Membranes 2019 - 9th International Conference on Textile Composites and Inflatable Structures, FORM and FORCE},
  isbn         = {9788412110104},
  issn         = {2518-6582},
  location     = {Barcelona, Spain},
  pages        = {509--515},
  publisher    = {International Center for Numerical Methods in Engineering},
  title        = {{FlexMaps Pavilion: A twisted arc made of mesostructured flat flexible panels}},
  year         = {2019},
}

@article{6919,
  author       = {Qi, Chao and Minin, Giulio Di and Vercellino, Irene and Wutz, Anton and Korkhov, Volodymyr M.},
  issn         = {23752548},
  journal      = {Science Advances},
  number       = {9},
  publisher    = {American Association for the Advancement of Science},
  title        = {{Structural basis of sterol recognition by human hedgehog receptor PTCH1}},
  doi          = {10.1126/sciadv.aaw6490},
  volume       = {5},
  year         = {2019},
}

@article{6920,
  author       = {Artner, Christina and Benková, Eva},
  issn         = {1674-2052},
  journal      = {Molecular Plant},
  number       = {10},
  pages        = {1312--1314},
  publisher    = {Cell Press},
  title        = {{Ethylene and cytokinin - partners in root growth regulation}},
  doi          = {10.1016/j.molp.2019.09.003},
  volume       = {12},
  year         = {2019},
}

@inproceedings{6931,
  abstract     = {Consider a distributed system with n processors out of which f can be Byzantine faulty. In the
approximate agreement task, each processor i receives an input value xi and has to decide on an
output value yi such that
1. the output values are in the convex hull of the non-faulty processors’ input values,
2. the output values are within distance d of each other.


Classically, the values are assumed to be from an m-dimensional Euclidean space, where m ≥ 1.
In this work, we study the task in a discrete setting, where input values with some structure
expressible as a graph. Namely, the input values are vertices of a finite graph G and the goal is to
output vertices that are within distance d of each other in G, but still remain in the graph-induced
convex hull of the input values. For d = 0, the task reduces to consensus and cannot be solved with
a deterministic algorithm in an asynchronous system even with a single crash fault. For any d ≥ 1,
we show that the task is solvable in asynchronous systems when G is chordal and n > (ω + 1)f,
where ω is the clique number of G. In addition, we give the first Byzantine-tolerant algorithm for a
variant of lattice agreement. For synchronous systems, we show tight resilience bounds for the exact
variants of these and related tasks over a large class of combinatorial structures.},
  author       = {Nowak, Thomas and Rybicki, Joel},
  booktitle    = {33rd International Symposium on Distributed Computing},
  keywords     = {consensus, approximate agreement, Byzantine faults, chordal graphs, lattice agreement},
  location     = {Budapest, Hungary},
  pages        = {29:1----29:17},
  publisher    = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
  title        = {{Byzantine approximate agreement on graphs}},
  doi          = {10.4230/LIPICS.DISC.2019.29},
  volume       = {146},
  year         = {2019},
}

@inproceedings{6933,
  abstract     = {We design fast deterministic algorithms for distance computation in the CONGESTED CLIQUE model. Our key contributions include:

 - A (2+ε)-approximation for all-pairs shortest paths problem in O(log²n / ε) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model.
 - A (1+ε)-approximation for multi-source shortest paths problem from O(√n) sources in O(log² n / ε) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size.

Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in Õ(n^{1/6}) rounds.},
  author       = {Censor-Hillel, Keren and Dory, Michal and Korhonen, Janne and Leitersdorf, Dean},
  booktitle    = {Proceedings of the 2019 ACM Symposium on Principles of Distributed Computin},
  isbn         = {9781450362177},
  location     = {Toronto, ON, Canada},
  pages        = {74--83},
  publisher    = {ACM},
  title        = {{Fast approximate shortest paths in the congested clique}},
  doi          = {10.1145/3293611.3331633},
  year         = {2019},
}

@inproceedings{6935,
  abstract     = {This paper investigates the power of preprocessing in the CONGEST model. Schmid and Suomela (ACM HotSDN 2013) introduced the SUPPORTED CONGEST model to study the application of distributed algorithms in Software-Defined Networks (SDNs). In this paper, we show that a large class of lower bounds in the CONGEST model still hold in the SUPPORTED model, highlighting the robustness of these bounds. This also raises the question how much does
preprocessing help in the CONGEST model.},
  author       = {Foerster, Klaus-Tycho and Korhonen, Janne and Rybicki, Joel and Schmid, Stefan},
  booktitle    = {Proceedings of the 2019 ACM Symposium on Principles of Distributed Computing},
  isbn         = {9781450362177},
  location     = {Toronto, ON, Canada},
  pages        = {259--261},
  publisher    = {ACM},
  title        = {{Does preprocessing help under congestion?}},
  doi          = {10.1145/3293611.3331581},
  year         = {2019},
}

@article{6936,
  abstract     = {A key challenge for community ecology is to understand to what extent observational data can be used to infer the underlying community assembly processes. As different processes can lead to similar or even identical patterns, statistical analyses of non‐manipulative observational data never yield undisputable causal inference on the underlying processes. Still, most empirical studies in community ecology are based on observational data, and hence understanding under which circumstances such data can shed light on assembly processes is a central concern for community ecologists. We simulated a spatial agent‐based model that generates variation in metacommunity dynamics across multiple axes, including the four classic metacommunity paradigms as special cases. We further simulated a virtual ecologist who analysed snapshot data sampled from the simulations using eighteen output metrics derived from beta‐diversity and habitat variation indices, variation partitioning and joint species distribution modelling. Our results indicated two main axes of variation in the output metrics. The first axis of variation described whether the landscape has patchy or continuous variation, and thus was essentially independent of the properties of the species community. The second axis of variation related to the level of predictability of the metacommunity. The most predictable communities were niche‐based metacommunities inhabiting static landscapes with marked environmental heterogeneity, such as metacommunities following the species sorting paradigm or the mass effects paradigm. The most unpredictable communities were neutral‐based metacommunities inhabiting dynamics landscapes with little spatial heterogeneity, such as metacommunities following the neutral or patch sorting paradigms. The output metrics from joint species distribution modelling yielded generally the highest resolution to disentangle among the simulated scenarios. Yet, the different types of statistical approaches utilized in this study carried complementary information, and thus our results suggest that the most comprehensive evaluation of metacommunity structure can be obtained by combining them.
},
  author       = {Ovaskainen, Otso and Rybicki, Joel and Abrego, Nerea},
  issn         = {1600-0587},
  journal      = {Ecography},
  number       = {11},
  pages        = {1877--1886},
  publisher    = {Wiley},
  title        = {{What can observational data reveal about metacommunity processes?}},
  doi          = {10.1111/ecog.04444},
  volume       = {42},
  year         = {2019},
}

@article{6940,
  abstract     = {We study the effect of a linear tunneling coupling between two-dimensional systems, each separately
exhibiting the topological Berezinskii-Kosterlitz-Thouless (BKT) transition. In the uncoupled limit, there
are two phases: one where the one-body correlation functions are algebraically decaying and the other with
exponential decay. When the linear coupling is turned on, a third BKT-paired phase emerges, in which one-body correlations are exponentially decaying, while two-body correlation functions exhibit power-law
decay. We perform numerical simulations in the paradigmatic case of two coupled XY models at finite
temperature, finding evidences that for any finite value of the interlayer coupling, the BKT-paired phase is
present. We provide a picture of the phase diagram using a renormalization group approach.},
  author       = {Bighin, Giacomo and Defenu, Nicolò and Nándori, István and Salasnich, Luca and Trombettoni, Andrea},
  issn         = {1079-7114},
  journal      = {Physical Review Letters},
  number       = {10},
  publisher    = {American Physical Society},
  title        = {{Berezinskii-Kosterlitz-Thouless paired phase in coupled XY models}},
  doi          = {10.1103/physrevlett.123.100601},
  volume       = {123},
  year         = {2019},
}

@inproceedings{6942,
  abstract     = {Graph games and Markov decision processes (MDPs) are standard models in reactive synthesis and verification of probabilistic systems with nondeterminism. The class of   𝜔 -regular winning conditions; e.g., safety, reachability, liveness, parity conditions; provides a robust and expressive specification formalism for properties that arise in analysis of reactive systems. The resolutions of nondeterminism in games and MDPs are represented as strategies, and we consider succinct representation of such strategies. The decision-tree data structure from machine learning retains the flavor of decisions of strategies and allows entropy-based minimization to obtain succinct trees. However, in contrast to traditional machine-learning problems where small errors are allowed, for winning strategies in graph games and MDPs no error is allowed, and the decision tree must represent the entire strategy. In this work we propose decision trees with linear classifiers for representation of strategies in graph games and MDPs. We have implemented strategy representation using this data structure and we present experimental results for problems on graph games and MDPs, which show that this new data structure presents a much more efficient strategy representation as compared to standard decision trees.},
  author       = {Ashok, Pranav and Brázdil, Tomáš and Chatterjee, Krishnendu and Křetínský, Jan and Lampert, Christoph and Toman, Viktor},
  booktitle    = {16th International Conference on Quantitative Evaluation of Systems},
  isbn         = {9783030302801},
  issn         = {0302-9743},
  location     = {Glasgow, United Kingdom},
  pages        = {109--128},
  publisher    = {Springer Nature},
  title        = {{Strategy representation by decision trees with linear classifiers}},
  doi          = {10.1007/978-3-030-30281-8_7},
  volume       = {11785},
  year         = {2019},
}

@article{6943,
  abstract     = {Plants as sessile organisms are constantly under attack by herbivores, rough environmental situations, or mechanical pressure. These challenges often lead to the induction of wounds or destruction of already specified and developed tissues. Additionally, wounding makes plants vulnerable to invasion by pathogens, which is why wound signalling often triggers specific defence responses. To stay competitive or, eventually, survive under these circumstances, plants need to regenerate efficiently, which in rigid, tissue migration-incompatible plant tissues requires post-embryonic patterning and organogenesis. Now, several studies used laser-assisted single cell ablation in the Arabidopsis root tip as a minimal wounding proxy. Here, we discuss their findings and put them into context of a broader spectrum of wound signalling, pathogen responses and tissue as well as organ regeneration.},
  author       = {Hörmayer, Lukas and Friml, Jiří},
  issn         = {1369-5266},
  journal      = {Current Opinion in Plant Biology},
  pages        = {124--130},
  publisher    = {Elsevier},
  title        = {{Targeted cell ablation-based insights into wound healing and restorative patterning}},
  doi          = {10.1016/j.pbi.2019.08.006},
  volume       = {52},
  year         = {2019},
}

@phdthesis{6947,
  abstract     = {Lymph nodes  are es s ential organs  of the immune  s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular  cells (FRCs) are  the  main  stromal  cells and  form  a sponge-like extracellular matrix network,   called  conduits ,  which  they   thems elves   enwrap   and  contract.  Lymph,  containing  s oluble  antigens ,  arrive in  lymph  nodes  via afferent lymphatic  vessels that  connect  to  the  s ubcaps ular  s inus   and  conduit  network.  According  to  the  current  paradigm,  the  conduit  network   dis tributes   afferent  lymph  through   lymph  nodes   and  thus   provides   acces s   for  immune  cells to lymph-borne  antigens. An  elas tic  caps ule  s urrounds   the  organ  and  confines   the immune  cells and  FRC  network.   Lymph   nodes   are  completely  packed  with  lymphocytes   and  lymphocyte  numbers  directly  dictates  the size  of  the  organ.  Although  lymphocytes   cons tantly  enter  and  leave  the  lymph  node,  its   s ize  remains   remarkedly   s table  under  homeostatic conditions. It is only partly known  how the cellularity and s ize of the lymph node is regulated and  how  the  lymph  node  is able to swell in inflammation.  The role of the FRC network   in  lymph  node   s welling  and  trans fer  of  fluids   are  inves tigated in  this   thes is.  Furthermore,   we  s tudied  what  trafficking  routes   are  us ed  by  cancer  cells   in  lymph  nodes   to  form  distal metastases.We examined the role of a mechanical feedback in regulation of lymph  node swelling. Using parallel plate compression  and UV-las er  cutting  experiments   we  dis s ected  the  mechanical  force dynamics  of the whole lymph  node, and individually for FRCs  and the  caps ule. Physical forces   generated  by  packed  lymphocytes   directly  affect  the  tens ion  on  the  FRC  network  and  capsule,  which  increases  its  resistance  to   swelling.  This  implies  a  feedback  mechanism  between   tis s ue   pres s ure   and   ability   of   lymphocytes    to   enter   the   organ.   Following   inflammation,  the  lymph  node  swells ∼10 fold in two weeks . Yet, what  is  the role  for tens ion on  the  FRC  network   and  caps ule,  and  how  are  lymphocytes   able  to  enter  in  conditions  that resist swelling remain open ques tions . We s how that tens ion on the FRC network is  important to  limit  the  swelling  rate  of  the  organ  so  that  the  FRC  network  can  grow  in  a  coordinated  fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates  and a dis organized FRC network  in the inflamed lymph  node. Growth  of the FRC network  in  turn  is   expected  to  releas e  tens ion  on  thes e  s tructures   and  lowers   the  res is tance  to  swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of  swelling coincides   with  a  thickening  of  the  caps ule,  which  forms   a  thick  res is tant  band  around  the organ and lowers  tens ion on the FRC network  to form a new force equilibrium.The  FRC  and  conduit   network   are  further   believed  to  be  a  privileged  s ite  of  s oluble  information  within  the  lymph  node,  although  many  details   remain  uns olved.  We  s how  by  3D  ultra-recons truction   that  FRCs   and  antigen  pres enting  cells   cover  the  s urface  of  conduit  s ys tem for more  than 99% and we dis cus s  the implications  for s oluble information  exchangeat the conduit level.Finally, there  is an ongoing debate in the cancer field whether and how cancer cells  in lymph nodes   s eed  dis tal  metas tas es .  We  s how  that  cancer  cells   infus ed  into  the  lymph  node  can  utilize trafficking routes of immune  cells and  rapidly  migrate  to  blood  vessels. Once  in  the  blood circulation,  these cells are able to form  metastases in distal tissues.},
  author       = {Assen, Frank P},
  issn         = {2663-337X},
  pages        = {142},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking}},
  doi          = {10.15479/AT:ISTA:6947},
  year         = {2019},
}

