@article{9549,
  abstract     = {AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. },
  author       = {Zhang, Danyang and Watson, Jake and Matthews, Peter M. and Cais, Ondrej and Greger, Ingo H.},
  issn         = {1476-4687},
  journal      = {Nature},
  pages        = {454--458},
  publisher    = {Springer Nature},
  title        = {{Gating and modulation of a hetero-octameric AMPA glutamate receptor}},
  doi          = {10.1038/s41586-021-03613-0},
  volume       = {594},
  year         = {2021},
}

@article{9569,
  abstract     = {We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values.},
  author       = {Dar, M. S. and Akram, Khush Bakhat and Sohail, Ayesha and Arif, Fatima and Zabihi, Fatemeh and Yang, Shengyuan and Munir, Shamsa and Zhu, Meifang and Abid, M. and Nauman, Muhammad},
  issn         = {2046-2069},
  journal      = {RSC Advances},
  number       = {35},
  pages        = {21702--21715},
  publisher    = {Royal Society of Chemistry},
  title        = {{Heat induction in two-dimensional graphene–Fe3O4 nanohybrids for magnetic hyperthermia applications with artificial neural network modeling}},
  doi          = {10.1039/d1ra03428f},
  volume       = {11},
  year         = {2021},
}

@article{9570,
  abstract     = {We present conductance-matrix measurements in long, three-terminal hybrid superconductor-semiconductor nanowires, and compare with theoretical predictions of a magnetic-field-driven, topological quantum phase transition. By examining the nonlocal conductance, we identify the closure of the excitation gap in the bulk of the semiconductor before the emergence of zero-bias peaks, ruling out spurious gap-closure signatures from localized states. We observe that after the gap closes, nonlocal signals and zero-bias peaks fluctuate strongly at both ends, inconsistent with a simple picture of clean topological superconductivity.},
  author       = {Puglia, Denise and Martinez, E. A. and Ménard, G. C. and Pöschl, A. and Gronin, S. and Gardner, G. C. and Kallaher, R. and Manfra, M. J. and Marcus, C. M. and Higginbotham, Andrew P and Casparis, L.},
  issn         = {2469-9969},
  journal      = {Physical Review B},
  number       = {23},
  publisher    = {American Physical Society},
  title        = {{Closing of the induced gap in a hybrid superconductor-semiconductor nanowire}},
  doi          = {10.1103/PhysRevB.103.235201},
  volume       = {103},
  year         = {2021},
}

@article{9571,
  abstract     = {As the size and complexity of models and datasets grow, so does the need for communication-efficient variants of stochastic gradient descent that can be deployed to perform parallel model training. One popular communication-compression method for data-parallel SGD is QSGD (Alistarh et al., 2017), which quantizes and encodes gradients to reduce communication costs. The baseline variant of QSGD provides strong theoretical guarantees, however, for practical purposes, the authors proposed a heuristic variant which we call QSGDinf, which demonstrated impressive empirical gains for distributed training of large neural networks. In this paper, we build on this work to propose a new gradient quantization scheme, and show that it has both stronger theoretical guarantees than QSGD, and matches and exceeds the empirical performance of the QSGDinf heuristic and of other compression methods.},
  author       = {Ramezani-Kebrya, Ali and Faghri, Fartash and Markov, Ilya and Aksenov, Vitalii and Alistarh, Dan-Adrian and Roy, Daniel M.},
  issn         = {1533-7928},
  journal      = {Journal of Machine Learning Research},
  number       = {114},
  pages        = {1−43},
  publisher    = {Journal of Machine Learning Research},
  title        = {{NUQSGD: Provably communication-efficient data-parallel SGD via nonuniform quantization}},
  volume       = {22},
  year         = {2021},
}

@inproceedings{9592,
  abstract     = {The convex grabbing game is a game where two players, Alice and Bob, alternate taking extremal points from the convex hull of a point set on the plane. Rational weights are given to the points. The goal of each player is to maximize the total weight over all points that they obtain. We restrict the setting to the case of binary weights. We show a construction of an arbitrarily large odd-sized point set that allows Bob to obtain almost 3/4 of the total weight. This construction answers a question asked by Matsumoto, Nakamigawa, and Sakuma in [Graphs and Combinatorics, 36/1 (2020)]. We also present an arbitrarily large even-sized point set where Bob can obtain the entirety of the total weight. Finally, we discuss conjectures about optimum moves in the convex grabbing game for both players in general.},
  author       = {Dvorak, Martin and Nicholson, Sara},
  booktitle    = {Proceedings of the 33rd Canadian Conference on Computational Geometry},
  keywords     = {convex grabbing game, graph grabbing game, combinatorial game, convex geometry},
  location     = {Halifax, NS, Canada; Virtual},
  publisher    = {Canadian Conference on Computational Geometry},
  title        = {{Massively winning configurations in the convex grabbing game on the plane}},
  year         = {2021},
}

@article{9602,
  abstract     = {An ordered graph is a graph with a linear ordering on its vertex set. We prove that for every positive integer k, there exists a constant ck > 0 such that any ordered graph G on n vertices with the property that neither G nor its complement contains an induced monotone path of size k, has either a clique or an independent set of size at least n^ck . This strengthens a result of Bousquet, Lagoutte, and Thomassé, who proved the analogous result for unordered graphs.
A key idea of the above paper was to show that any unordered graph on n vertices that does not contain an induced path of size k, and whose maximum degree is at most c(k)n for some small c(k) > 0, contains two disjoint linear size subsets with no edge between them. This approach fails for ordered graphs, because the analogous statement is false for k ≥ 3, by a construction of Fox. We provide some further examples showing that this statement also fails for ordered graphs avoiding other ordered trees.},
  author       = {Pach, János and Tomon, István},
  issn         = {0095-8956},
  journal      = {Journal of Combinatorial Theory. Series B},
  pages        = {21--37},
  publisher    = {Elsevier},
  title        = {{Erdős-Hajnal-type results for monotone paths}},
  doi          = {10.1016/j.jctb.2021.05.004},
  volume       = {151},
  year         = {2021},
}

@inproceedings{9604,
  abstract     = {Generalizing Lee’s inductive argument for counting the cells of higher order Voronoi tessellations in ℝ² to ℝ³, we get precise relations in terms of Morse theoretic quantities for piecewise constant functions on planar arrangements. Specifically, we prove that for a generic set of n ≥ 5 points in ℝ³, the number of regions in the order-k Voronoi tessellation is N_{k-1} - binom(k,2)n + n, for 1 ≤ k ≤ n-1, in which N_{k-1} is the sum of Euler characteristics of these function’s first k-1 sublevel sets. We get similar expressions for the vertices, edges, and polygons of the order-k Voronoi tessellation.},
  author       = {Biswas, Ranita and Cultrera di Montesano, Sebastiano and Edelsbrunner, Herbert and Saghafian, Morteza},
  booktitle    = {Leibniz International Proceedings in Informatics},
  isbn         = {9783959771849},
  issn         = {1868-8969},
  location     = {Online},
  publisher    = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
  title        = {{Counting cells of order-k voronoi tessellations in ℝ<sup>3</sup> with morse theory}},
  doi          = {10.4230/LIPIcs.SoCG.2021.16},
  volume       = {189},
  year         = {2021},
}

@inproceedings{9605,
  abstract     = {Given a finite set A ⊂ ℝ^d, let Cov_{r,k} denote the set of all points within distance r to at least k points of A. Allowing r and k to vary, we obtain a 2-parameter family of spaces that grow larger when r increases or k decreases, called the multicover bifiltration. Motivated by the problem of computing the homology of this bifiltration, we introduce two closely related combinatorial bifiltrations, one polyhedral and the other simplicial, which are both topologically equivalent to the multicover bifiltration and far smaller than a Čech-based model considered in prior work of Sheehy. Our polyhedral construction is a bifiltration of the rhomboid tiling of Edelsbrunner and Osang, and can be efficiently computed using a variant of an algorithm given by these authors as well. Using an implementation for dimension 2 and 3, we provide experimental results. Our simplicial construction is useful for understanding the polyhedral construction and proving its correctness. },
  author       = {Corbet, René and Kerber, Michael and Lesnick, Michael and Osang, Georg F},
  booktitle    = {Leibniz International Proceedings in Informatics},
  isbn         = {9783959771849},
  issn         = {1868-8969},
  location     = {Online},
  publisher    = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
  title        = {{Computing the multicover bifiltration}},
  doi          = {10.4230/LIPIcs.SoCG.2021.27},
  volume       = {189},
  year         = {2021},
}

@article{9606,
  abstract     = {Sound propagation is a macroscopic manifestation of the interplay between the equilibrium thermodynamics and the dynamical transport properties of fluids. Here, for a two-dimensional system of ultracold fermions, we calculate the first and second sound velocities across the whole BCS-BEC crossover, and we analyze the system response to an external perturbation. In the low-temperature regime we reproduce the recent measurements [Phys. Rev. Lett. 124, 240403 (2020)] of the first sound velocity, which, due to the decoupling of density and entropy fluctuations, is the sole mode excited by a density probe. Conversely, a heat perturbation excites only the second sound, which, being sensitive to the superfluid depletion, vanishes in the deep BCS regime and jumps discontinuously to zero at the Berezinskii-Kosterlitz-Thouless superfluid transition. A mixing between the modes occurs only in the finite-temperature BEC regime, where our theory converges to the purely bosonic results.},
  author       = {Tononi, A. and Cappellaro, Alberto and Bighin, Giacomo and Salasnich, L.},
  issn         = {2469-9934},
  journal      = {Physical Review A},
  number       = {6},
  publisher    = {American Physical Society},
  title        = {{Propagation of first and second sound in a two-dimensional Fermi superfluid}},
  doi          = {10.1103/PhysRevA.103.L061303},
  volume       = {103},
  year         = {2021},
}

@article{9618,
  abstract     = {The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science.},
  author       = {Bluvstein, D. and Omran, A. and Levine, H. and Keesling, A. and Semeghini, G. and Ebadi, S. and Wang, T. T. and Michailidis, Alexios and Maskara, N. and Ho, W. W. and Choi, S. and Serbyn, Maksym and Greiner, M. and Vuletić, V. and Lukin, M. D.},
  issn         = {1095-9203},
  journal      = {Science},
  keywords     = {Multidisciplinary},
  number       = {6536},
  pages        = {1355--1359},
  publisher    = {AAAS},
  title        = {{Controlling quantum many-body dynamics in driven Rydberg atom arrays}},
  doi          = {10.1126/science.abg2530},
  volume       = {371},
  year         = {2021},
}

@inproceedings{9620,
  abstract     = {In this note, we introduce a distributed twist on the classic coupon collector problem: a set of m collectors wish to each obtain a set of n coupons; for this, they can each sample coupons uniformly at random, but can also meet in pairwise interactions, during which they can exchange coupons. By doing so, they hope to reduce the number of coupons that must be sampled by each collector in order to obtain a full set. This extension is natural when considering real-world manifestations of the coupon collector phenomenon, and has been remarked upon and studied empirically (Hayes and Hannigan 2006, Ahmad et al. 2014, Delmarcelle 2019).

We provide the first theoretical analysis for such a scenario. We find that “coupon collecting with friends” can indeed significantly reduce the number of coupons each collector must sample, and raises interesting connections to the more traditional variants of the problem. While our analysis is in most cases asymptotically tight, there are several open questions raised, regarding finer-grained analysis of both “coupon collecting with friends,” and of a long-studied variant of the original problem in which a collector requires multiple full sets of coupons.},
  author       = {Alistarh, Dan-Adrian and Davies, Peter},
  booktitle    = {Structural Information and Communication Complexity},
  isbn         = {9783030795269},
  issn         = {1611-3349},
  location     = {Wrocław, Poland},
  pages        = {3--12},
  publisher    = {Springer Nature},
  title        = {{Collecting coupons is faster with friends}},
  doi          = {10.1007/978-3-030-79527-6_1},
  volume       = {12810},
  year         = {2021},
}

@article{9626,
  abstract     = {SnSe, a wide-bandgap semiconductor, has attracted significant attention from the thermoelectric (TE) community due to its outstanding TE performance deriving from the ultralow thermal conductivity and advantageous electronic structures. Here, we promoted the TE performance of n-type SnSe polycrystals through bandgap engineering and vacancy compensation. We found that PbTe can significantly reduce the wide bandgap of SnSe to reduce the impurity transition energy, largely enhancing the carrier concentration. Also, PbTe-induced crystal symmetry promotion increases the carrier mobility, preserving large Seebeck coefficient. Consequently, a maximum ZT of ∼1.4 at 793 K is obtained in Br doped SnSe–13%PbTe. Furthermore, we found that extra Sn in n-type SnSe can compensate for the intrinsic Sn vacancies and form electron donor-like metallic Sn nanophases. The Sn nanophases near the grain boundary could also reduce the intergrain energy barrier which largely enhances the carrier mobility. As a result, a maximum ZT value of ∼1.7 at 793 K and an average ZT (ZTave) of ∼0.58 in 300–793 K are achieved in Br doped Sn1.08Se–13%PbTe. Our findings provide a novel strategy to promote the TE performance in wide-bandgap semiconductors.},
  author       = {Su, Lizhong and Hong, Tao and Wang, Dongyang and Wang, Sining and Qin, Bingchao and Zhang, Mengmeng and Gao, Xiang and Chang, Cheng and Zhao, Li Dong},
  issn         = {2542-5293},
  journal      = {Materials Today Physics},
  publisher    = {Elsevier},
  title        = {{Realizing high doping efficiency and thermoelectric performance in n-type SnSe polycrystals via bandgap engineering and vacancy compensation}},
  doi          = {10.1016/j.mtphys.2021.100452},
  volume       = {20},
  year         = {2021},
}

@article{9627,
  abstract     = {We compute the deficiency spaces of operators of the form 𝐻𝐴⊗̂ 𝐼+𝐼⊗̂ 𝐻𝐵, for symmetric 𝐻𝐴 and self-adjoint 𝐻𝐵. This enables us to construct self-adjoint extensions (if they exist) by means of von Neumann's theory. The structure of the deficiency spaces for this case was asserted already in Ibort et al. [Boundary dynamics driven entanglement, J. Phys. A: Math. Theor. 47(38) (2014) 385301], but only proven under the restriction of 𝐻𝐵 having discrete, non-degenerate spectrum.},
  author       = {Lenz, Daniel and Weinmann, Timon and Wirth, Melchior},
  issn         = {1464-3839},
  journal      = {Proceedings of the Edinburgh Mathematical Society},
  number       = {3},
  pages        = {443--447},
  publisher    = {Cambridge University Press},
  title        = {{Self-adjoint extensions of bipartite Hamiltonians}},
  doi          = {10.1017/S0013091521000080},
  volume       = {64},
  year         = {2021},
}

@article{9629,
  abstract     = {Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.},
  author       = {Yang, Qiutan and Xue, Shi-lei and Chan, Chii Jou and Rempfler, Markus and Vischi, Dario and Maurer-Gutierrez, Francisca and Hiiragi, Takashi and Hannezo, Edouard B and Liberali, Prisca},
  issn         = {1476-4679},
  journal      = {Nature Cell Biology},
  pages        = {733–744},
  publisher    = {Springer Nature},
  title        = {{Cell fate coordinates mechano-osmotic forces in intestinal crypt formation}},
  doi          = {10.1038/s41556-021-00700-2},
  volume       = {23},
  year         = {2021},
}

@misc{9636,
  author       = {Higginbotham, Andrew P},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Data for "Breakdown of induced p ± ip pairing in a superconductor-semiconductor hybrid"}},
  year         = {2021},
}

@article{9641,
  abstract     = {At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.},
  author       = {Fredes, Felipe and Shigemoto, Ryuichi},
  issn         = {1095-9564},
  journal      = {Neurobiology of Learning and Memory},
  publisher    = {Elsevier},
  title        = {{The role of hippocampal mossy cells in novelty detection}},
  doi          = {10.1016/j.nlm.2021.107486},
  volume       = {183},
  year         = {2021},
}

@inproceedings{9645,
  abstract     = {We consider the fundamental problem of reachability analysis over imperative programs with real variables. Previous works that tackle reachability are either unable to handle programs consisting of general loops (e.g. symbolic execution), or lack completeness guarantees (e.g. abstract interpretation), or are not automated (e.g. incorrectness logic). In contrast, we propose a novel approach for reachability analysis that can handle general and complex loops, is complete, and can be entirely automated for a wide family of programs. Through the notion of Inductive Reachability Witnesses (IRWs), our approach extends ideas from both invariant generation and termination to reachability analysis.

We first show that our IRW-based approach is sound and complete for reachability analysis of imperative programs. Then, we focus on linear and polynomial programs and develop automated methods for synthesizing linear and polynomial IRWs. In the linear case, we follow the well-known approaches using Farkas' Lemma. Our main contribution is in the polynomial case, where we present a push-button semi-complete algorithm. We achieve this using a novel combination of classical theorems in real algebraic geometry, such as Putinar's Positivstellensatz and Hilbert's Strong Nullstellensatz. Finally, our experimental results show we can prove complex reachability objectives over various benchmarks that were beyond the reach of previous methods.},
  author       = {Asadi, Ali and Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar and Mahdavi, Mohammad},
  booktitle    = {Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation},
  isbn         = {9781450383912},
  location     = {Online},
  pages        = {772--787},
  publisher    = {Association for Computing Machinery},
  title        = {{Polynomial reachability witnesses via Stellensätze}},
  doi          = {10.1145/3453483.3454076},
  year         = {2021},
}

@inproceedings{9646,
  abstract     = {We consider the fundamental problem of deriving quantitative bounds on the probability that a given assertion is violated in a probabilistic program. We provide automated algorithms that obtain both lower and upper bounds on the assertion violation probability. The main novelty of our approach is that we prove new and dedicated fixed-point theorems which serve as the theoretical basis of our algorithms and enable us to reason about assertion violation bounds in terms of pre and post fixed-point functions. To synthesize such fixed-points, we devise algorithms that utilize a wide range of mathematical tools, including repulsing ranking supermartingales, Hoeffding's lemma, Minkowski decompositions, Jensen's inequality, and convex optimization. On the theoretical side, we provide (i) the first automated algorithm for lower-bounds on assertion violation probabilities, (ii) the first complete algorithm for upper-bounds of exponential form in affine programs, and (iii) provably and significantly tighter upper-bounds than the previous approaches. On the practical side, we show our algorithms can handle a wide variety of programs from the literature and synthesize bounds that are remarkably tighter than previous results, in some cases by thousands of orders of magnitude.},
  author       = {Wang, Jinyi and Sun, Yican and Fu, Hongfei and Chatterjee, Krishnendu and Goharshady, Amir Kafshdar},
  booktitle    = {Proceedings of the 42nd ACM SIGPLAN International Conference on Programming Language Design and Implementation},
  isbn         = {9781450383912},
  location     = {Online},
  pages        = {1171--1186},
  publisher    = {Association for Computing Machinery},
  title        = {{Quantitative analysis of assertion violations in probabilistic programs}},
  doi          = {10.1145/3453483.3454102},
  year         = {2021},
}

@article{9647,
  abstract     = {Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.},
  author       = {Petrov, Tatjana and Igler, Claudia and Sezgin, Ali and Henzinger, Thomas A and Guet, Calin C},
  issn         = {0304-3975},
  journal      = {Theoretical Computer Science},
  pages        = {1--16},
  publisher    = {Elsevier},
  title        = {{Long lived transients in gene regulation}},
  doi          = {10.1016/j.tcs.2021.05.023},
  volume       = {893},
  year         = {2021},
}

@article{9656,
  abstract     = {Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underly differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, and a crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment.},
  author       = {Han, Huibin and Adamowski, Maciek and Qi, Linlin and Alotaibi, SS and Friml, Jiří},
  issn         = {1469-8137},
  journal      = {New Phytologist},
  number       = {2},
  pages        = {510--522},
  publisher    = {Wiley},
  title        = {{PIN-mediated polar auxin transport regulations in plant tropic responses}},
  doi          = {10.1111/nph.17617},
  volume       = {232},
  year         = {2021},
}

