@article{8818, abstract = {The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.}, author = {Ramirez Villegas, Juan F and Besserve, Michel and Murayama, Yusuke and Evrard, Henry C. and Oeltermann, Axel and Logothetis, Nikos K.}, issn = {14764687}, journal = {Nature}, number = {7840}, pages = {96--102}, publisher = {Springer Nature}, title = {{Coupling of hippocampal theta and ripples with pontogeniculooccipital waves}}, doi = {10.1038/s41586-020-2914-4}, volume = {589}, year = {2021}, } @article{8824, abstract = {Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface.}, author = {Marquès-Bueno, MM and Armengot, L and Noack, LC and Bareille, J and Rodriguez Solovey, Lesia and Platre, MP and Bayle, V and Liu, M and Opdenacker, D and Vanneste, S and Möller, BK and Nimchuk, ZL and Beeckman, T and Caño-Delgado, AI and Friml, Jiří and Jaillais, Y}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, publisher = {Elsevier}, title = {{Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism}}, doi = {10.1016/j.cub.2020.10.011}, volume = {31}, year = {2021}, } @article{8909, abstract = {Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits have moved into the focus of interest due to the ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled X and Z-rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1μs which we extend beyond 15μs with echo techniques. These results show that Ge hole singlet triplet qubits outperform their electronic Si and GaAs based counterparts in speed and coherence, respectively. In addition, they are on par with Ge single spin qubits, but can be operated at much lower fields underlining their potential for on chip integration with superconducting technologies.}, author = {Jirovec, Daniel and Hofmann, Andrea C and Ballabio, Andrea and Mutter, Philipp M. and Tavani, Giulio and Botifoll, Marc and Crippa, Alessandro and Kukucka, Josip and Sagi, Oliver and Martins, Frederico and Saez Mollejo, Jaime and Prieto Gonzalez, Ivan and Borovkov, Maksim and Arbiol, Jordi and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, issn = {1476-4660}, journal = {Nature Materials}, number = {8}, pages = {1106–1112}, publisher = {Springer Nature}, title = {{A singlet triplet hole spin qubit in planar Ge}}, doi = {10.1038/s41563-021-01022-2}, volume = {20}, year = {2021}, } @article{8910, abstract = {A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks—features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity.}, author = {Valentini, Marco and Peñaranda, Fernando and Hofmann, Andrea C and Brauns, Matthias and Hauschild, Robert and Krogstrup, Peter and San-Jose, Pablo and Prada, Elsa and Aguado, Ramón and Katsaros, Georgios}, issn = {10959203}, journal = {Science}, number = {6550}, publisher = {American Association for the Advancement of Science}, title = {{Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states}}, doi = {10.1126/science.abf1513}, volume = {373}, year = {2021}, } @article{8911, abstract = {In the worldwide endeavor for disruptive quantum technologies, germanium is emerging as a versatile material to realize devices capable of encoding, processing, or transmitting quantum information. These devices leverage special properties of the germanium valence-band states, commonly known as holes, such as their inherently strong spin-orbit coupling and the ability to host superconducting pairing correlations. In this Review, we initially introduce the physics of holes in low-dimensional germanium structures with key insights from a theoretical perspective. We then examine the material science progress underpinning germanium-based planar heterostructures and nanowires. We review the most significant experimental results demonstrating key building blocks for quantum technology, such as an electrically driven universal quantum gate set with spin qubits in quantum dots and superconductor-semiconductor devices for hybrid quantum systems. We conclude by identifying the most promising prospects toward scalable quantum information processing. }, author = {Scappucci, Giordano and Kloeffel, Christoph and Zwanenburg, Floris A. and Loss, Daniel and Myronov, Maksym and Zhang, Jian-Jun and Franceschi, Silvano De and Katsaros, Georgios and Veldhorst, Menno}, issn = {2058-8437}, journal = {Nature Reviews Materials}, pages = {926–943 }, publisher = {Springer Nature}, title = {{The germanium quantum information route}}, doi = {10.1038/s41578-020-00262-z}, volume = {6}, year = {2021}, } @article{8912, abstract = {For automata, synchronization, the problem of bringing an automaton to a particular state regardless of its initial state, is important. It has several applications in practice and is related to a fifty-year-old conjecture on the length of the shortest synchronizing word. Although using shorter words increases the effectiveness in practice, finding a shortest one (which is not necessarily unique) is NP-hard. For this reason, there exist various heuristics in the literature. However, high-quality heuristics such as SynchroP producing relatively shorter sequences are very expensive and can take hours when the automaton has tens of thousands of states. The SynchroP heuristic has been frequently used as a benchmark to evaluate the performance of the new heuristics. In this work, we first improve the runtime of SynchroP and its variants by using algorithmic techniques. We then focus on adapting SynchroP for many-core architectures, and overall, we obtain more than 1000× speedup on GPUs compared to naive sequential implementation that has been frequently used as a benchmark to evaluate new heuristics in the literature. We also propose two SynchroP variants and evaluate their performance.}, author = {Sarac, Naci E and Altun, Ömer Faruk and Atam, Kamil Tolga and Karahoda, Sertac and Kaya, Kamer and Yenigün, Hüsnü}, issn = {09574174}, journal = {Expert Systems with Applications}, number = {4}, publisher = {Elsevier}, title = {{Boosting expensive synchronizing heuristics}}, doi = {10.1016/j.eswa.2020.114203}, volume = {167}, year = {2021}, } @article{8927, abstract = {The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19.}, author = {Nardo, Alexander D. and Schneeweiss-Gleixner, Mathias and Bakail, May M and Dixon, Emmanuel D. and Lax, Sigurd F. and Trauner, Michael}, issn = {14783231}, journal = {Liver International}, number = {1}, pages = {20--32}, publisher = {Wiley}, title = {{Pathophysiological mechanisms of liver injury in COVID-19}}, doi = {10.1111/liv.14730}, volume = {41}, year = {2021}, } @article{8928, abstract = {Domestication is a human‐induced selection process that imprints the genomes of domesticated populations over a short evolutionary time scale and that occurs in a given demographic context. Reconstructing historical gene flow, effective population size changes and their timing is therefore of fundamental interest to understand how plant demography and human selection jointly shape genomic divergence during domestication. Yet, the comparison under a single statistical framework of independent domestication histories across different crop species has been little evaluated so far. Thus, it is unclear whether domestication leads to convergent demographic changes that similarly affect crop genomes. To address this question, we used existing and new transcriptome data on three crop species of Solanaceae (eggplant, pepper and tomato), together with their close wild relatives. We fitted twelve demographic models of increasing complexity on the unfolded joint allele frequency spectrum for each wild/crop pair, and we found evidence for both shared and species‐specific demographic processes between species. A convergent history of domestication with gene flow was inferred for all three species, along with evidence of strong reduction in the effective population size during the cultivation stage of tomato and pepper. The absence of any reduction in size of the crop in eggplant stands out from the classical view of the domestication process; as does the existence of a “protracted period” of management before cultivation. Our results also suggest divergent management strategies of modern cultivars among species as their current demography substantially differs. Finally, the timing of domestication is species‐specific and supported by the few historical records available.}, author = {Arnoux, Stéphanie and Fraisse, Christelle and Sauvage, Christopher}, issn = {14209101}, journal = {Journal of Evolutionary Biology}, number = {2}, pages = {270--283}, publisher = {Wiley}, title = {{Genomic inference of complex domestication histories in three Solanaceae species}}, doi = {10.1111/jeb.13723}, volume = {34}, year = {2021}, } @article{8931, abstract = {Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear. Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation. The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy.}, author = {Gelová, Zuzana and Gallei, Michelle C and Pernisová, Markéta and Brunoud, Géraldine and Zhang, Xixi and Glanc, Matous and Li, Lanxin and Michalko, Jaroslav and Pavlovicova, Zlata and Verstraeten, Inge and Han, Huibin and Hajny, Jakub and Hauschild, Robert and Čovanová, Milada and Zwiewka, Marta and Hörmayer, Lukas and Fendrych, Matyas and Xu, Tongda and Vernoux, Teva and Friml, Jiří}, issn = {0168-9452}, journal = {Plant Science}, keywords = {Agronomy and Crop Science, Plant Science, Genetics, General Medicine}, publisher = {Elsevier}, title = {{Developmental roles of auxin binding protein 1 in Arabidopsis thaliana}}, doi = {10.1016/j.plantsci.2020.110750}, volume = {303}, year = {2021}, } @phdthesis{8934, abstract = {In this thesis, we consider several of the most classical and fundamental problems in static analysis and formal verification, including invariant generation, reachability analysis, termination analysis of probabilistic programs, data-flow analysis, quantitative analysis of Markov chains and Markov decision processes, and the problem of data packing in cache management. We use techniques from parameterized complexity theory, polyhedral geometry, and real algebraic geometry to significantly improve the state-of-the-art, in terms of both scalability and completeness guarantees, for the mentioned problems. In some cases, our results are the first theoretical improvements for the respective problems in two or three decades.}, author = {Goharshady, Amir Kafshdar}, issn = {2663-337X}, pages = {278}, publisher = {Institute of Science and Technology Austria}, title = {{Parameterized and algebro-geometric advances in static program analysis}}, doi = {10.15479/AT:ISTA:8934}, year = {2021}, } @article{8940, abstract = {We quantise Whitney’s construction to prove the existence of a triangulation for any C^2 manifold, so that we get an algorithm with explicit bounds. We also give a new elementary proof, which is completely geometric.}, author = {Boissonnat, Jean-Daniel and Kachanovich, Siargey and Wintraecken, Mathijs}, issn = {1432-0444}, journal = {Discrete & Computational Geometry}, keywords = {Theoretical Computer Science, Computational Theory and Mathematics, Geometry and Topology, Discrete Mathematics and Combinatorics}, number = {1}, pages = {386--434}, publisher = {Springer Nature}, title = {{Triangulating submanifolds: An elementary and quantified version of Whitney’s method}}, doi = {10.1007/s00454-020-00250-8}, volume = {66}, year = {2021}, } @article{8966, abstract = {During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important prerequisite for the emergence of patterns within the developing organism is to establish asymmetries at various scales, ranging from individual cells to the entire embryo, eventually giving rise to the different body structures. This becomes especially apparent during gastrulation, when the earliest major lineage restriction events lead to the formation of the different germ layers. Traditionally, the unfolding of the developmental program from symmetry breaking to germ layer formation has been studied by dissecting the contributions of different signaling pathways and cellular rearrangements in the in vivo context of intact embryos. Recent efforts, using the intrinsic capacity of embryonic stem cells to self-assemble and generate embryo-like structures de novo, have opened new avenues for understanding the many ways by which an embryo can be built and the influence of extrinsic factors therein. Here, we discuss and compare divergent and conserved strategies leading to germ layer formation in embryos as compared to in vitro systems, their upstream molecular cascades and the role of extrinsic factors in this process.}, author = {Schauer, Alexandra and Heisenberg, Carl-Philipp J}, issn = {0012-1606}, journal = {Developmental Biology}, keywords = {Developmental Biology, Cell Biology, Molecular Biology}, pages = {71--81}, publisher = {Elsevier}, title = {{Reassembling gastrulation}}, doi = {10.1016/j.ydbio.2020.12.014}, volume = {474}, year = {2021}, } @article{8988, abstract = {The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite branching by regulating the small GTPase ARF6. Together with the motor protein KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity. However, what defines the function of ADAP1 and how its different roles are coordinated are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions. We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well as PI(3,4)P2 act as stop signals for this transport instead of being transported. We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity to catalyze GTP hydrolysis by ARF6. Together, our results support a model for the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates from the motor to inactivate ARF6, promoting dendrite branching.}, author = {Düllberg, Christian F and Auer, Albert and Canigova, Nikola and Loibl, Katrin and Loose, Martin}, issn = {10916490}, journal = {PNAS}, number = {1}, publisher = {National Academy of Sciences}, title = {{In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1}}, doi = {10.1073/pnas.2010054118}, volume = {118}, year = {2021}, } @article{8992, abstract = {The phytohormone auxin plays a central role in shaping plant growth and development. With decades of genetic and biochemical studies, numerous core molecular components and their networks, underlying auxin biosynthesis, transport, and signaling, have been identified. Notably, protein phosphorylation, catalyzed by kinases and oppositely hydrolyzed by phosphatases, has been emerging to be a crucial type of post-translational modification, regulating physiological and developmental auxin output at all levels. In this review, we comprehensively discuss earlier and recent advances in our understanding of genetics, biochemistry, and cell biology of the kinases and phosphatases participating in auxin action. We provide insights into the mechanisms by which reversible protein phosphorylation defines developmental auxin responses, discuss current challenges, and provide our perspectives on future directions involving the integration of the control of protein phosphorylation into the molecular auxin network.}, author = {Tan, Shutang and Luschnig, Christian and Friml, Jiří}, issn = {17529867}, journal = {Molecular Plant}, number = {1}, pages = {151--165}, publisher = {Elsevier}, title = {{Pho-view of auxin: Reversible protein phosphorylation in auxin biosynthesis, transport and signaling}}, doi = {10.1016/j.molp.2020.11.004}, volume = {14}, year = {2021}, } @article{8993, abstract = {N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism.}, author = {Abas, Lindy and Kolb, Martina and Stadlmann, Johannes and Janacek, Dorina P. and Lukic, Kristina and Schwechheimer, Claus and Sazanov, Leonid A and Mach, Lukas and Friml, Jiří and Hammes, Ulrich Z.}, issn = {10916490}, journal = {PNAS}, number = {1}, publisher = {National Academy of Sciences}, title = {{Naphthylphthalamic acid associates with and inhibits PIN auxin transporters}}, doi = {10.1073/pnas.2020857118}, volume = {118}, year = {2021}, } @article{8997, abstract = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions}, publisher = {Public Library of Science}, title = {{Minimal biophysical model of combined antibiotic action}}, doi = {10.1371/journal.pcbi.1008529}, volume = {17}, year = {2021}, } @article{8999, abstract = {In many basic shear flows, such as pipe, Couette, and channel flow, turbulence does not arise from an instability of the laminar state, and both dynamical states co-exist. With decreasing flow speed (i.e., decreasing Reynolds number) the fraction of fluid in laminar motion increases while turbulence recedes and eventually the entire flow relaminarizes. The first step towards understanding the nature of this transition is to determine if the phase change is of either first or second order. In the former case, the turbulent fraction would drop discontinuously to zero as the Reynolds number decreases while in the latter the process would be continuous. For Couette flow, the flow between two parallel plates, earlier studies suggest a discontinuous scenario. In the present study we realize a Couette flow between two concentric cylinders which allows studies to be carried out in large aspect ratios and for extensive observation times. The presented measurements show that the transition in this circular Couette geometry is continuous suggesting that former studies were limited by finite size effects. A further characterization of this transition, in particular its relation to the directed percolation universality class, requires even larger system sizes than presently available. }, author = {Avila, Kerstin and Hof, Björn}, issn = {1099-4300}, journal = {Entropy}, number = {1}, publisher = {MDPI}, title = {{Second-order phase transition in counter-rotating taylor-couette flow experiment}}, doi = {10.3390/e23010058}, volume = {23}, year = {2021}, } @article{6965, abstract = {The central object of investigation of this paper is the Hirzebruch class, a deformation of the Todd class, given by Hirzebruch (for smooth varieties). The generalization for singular varieties is due to Brasselet–Schürmann–Yokura. Following the work of Weber, we investigate its equivariant version for (possibly singular) toric varieties. The local decomposition of the Hirzebruch class to the fixed points of the torus action and a formula for the local class in terms of the defining fan are recalled. After this review part, we prove the positivity of local Hirzebruch classes for all toric varieties, thus proving false the alleged counterexample given by Weber.}, author = {Rychlewicz, Kamil P}, issn = {1469-2120}, journal = {Bulletin of the London Mathematical Society}, number = {2}, pages = {560--574}, publisher = {Wiley}, title = {{The positivity of local equivariant Hirzebruch class for toric varieties}}, doi = {10.1112/blms.12442}, volume = {53}, year = {2021}, } @misc{6995, abstract = {Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.}, author = {Samarasinghe, Ranmal A. and Miranda, Osvaldo and Buth, Jessie E. and Mitchell, Simon and Ferando, Isabella and Watanabe, Momoko and Kurdian, Arinnae and Golshani, Peyman and Plath, Kathrin and Lowry, William E. and Parent, Jack M. and Mody, Istvan and Novitch, Bennett G.}, issn = {1546-1726}, pages = {32}, publisher = {Springer Nature}, title = {{Identification of neural oscillations and epileptiform changes in human brain organoids}}, doi = {10.1038/s41593-021-00906-5}, volume = {24}, year = {2021}, } @article{7463, abstract = {Resting-state brain activity is characterized by the presence of neuronal avalanches showing absence of characteristic size. Such evidence has been interpreted in the context of criticality and associated with the normal functioning of the brain. A distinctive attribute of systems at criticality is the presence of long-range correlations. Thus, to verify the hypothesis that the brain operates close to a critical point and consequently assess deviations from criticality for diagnostic purposes, it is of primary importance to robustly and reliably characterize correlations in resting-state brain activity. Recent works focused on the analysis of narrow-band electroencephalography (EEG) and magnetoencephalography (MEG) signal amplitude envelope, showing evidence of long-range temporal correlations (LRTC) in neural oscillations. However, brain activity is a broadband phenomenon, and a significant piece of information useful to precisely discriminate between normal (critical) and pathological behavior (non-critical), may be encoded in the broadband spatio-temporal cortical dynamics. Here we propose to characterize the temporal correlations in the broadband brain activity through the lens of neuronal avalanches. To this end, we consider resting-state EEG and long-term MEG recordings, extract the corresponding neuronal avalanche sequences, and study their temporal correlations. We demonstrate that the broadband resting-state brain activity consistently exhibits long-range power-law correlations in both EEG and MEG recordings, with similar values of the scaling exponents. Importantly, although we observe that the avalanche size distribution depends on scale parameters, scaling exponents characterizing long-range correlations are quite robust. In particular, they are independent of the temporal binning (scale of analysis), indicating that our analysis captures intrinsic characteristics of the underlying dynamics. Because neuronal avalanches constitute a fundamental feature of neural systems with universal characteristics, the proposed approach may serve as a general, systems- and experiment-independent procedure to infer the existence of underlying long-range correlations in extended neural systems, and identify pathological behaviors in the complex spatio-temporal interplay of cortical rhythms.}, author = {Lombardi, Fabrizio and Shriki, Oren and Herrmann, Hans J and de Arcangelis, Lucilla}, issn = {1872-8286}, journal = {Neurocomputing}, pages = {657--666}, publisher = {Elsevier}, title = {{Long-range temporal correlations in the broadband resting state activity of the human brain revealed by neuronal avalanches}}, doi = {10.1016/j.neucom.2020.05.126}, volume = {461}, year = {2021}, }